3. 3
acib – Innovations from Nature ........................................................................... 03
About acib – Fields of Expertise .......................................................................... 06
Homage to Coco Chanel .................................................................................... 09
Liver in a Test Tube as a New Pharma Key Technology ......................................... 10
„Pine Aroma“ Against Beetle Invasion ................................................................ 13
Greenhouse Gas CO2
as a Raw Material: Aspirin From Carbon Dioxide................. 15
Cell Aging Delayed ............................................................................................. 17
Millions of Liters of Juice from One Grapefruit .................................................... 19
Advanced Biofuels Without Food Use ................................................................. 20
Enzymes from Austria Revolutionize the World of Paints ..................................... 22
New Value for Old Plastics .................................................................................. 25
“Enzyme-Google” Reveals Hidden Possibilities of Nature .................................... 27
The Sugar Side of Biotechnology ......................................................................... 28
Plant Defense as a Biotech Tool ........................................................................... 31
High-Temperature Reductase for Organic Synthesis Available .............................. 32
Styrian Horse Radish Visualizes Active Enzymes ................................................... 35
Bodyguards for Precious Seeds ............................................................................ 36
Enzymes Against Fungal Toxins in Animal Feed ................................................... 38
Virus in the Service of Health .............................................................................. 40
Transparent Bioprocesses by Analyzing the Respiratory Air of Microorganisms .... 42
Newly Discovered Metabolism Certifies Evolutionary Advantage for Yeast .......... 44
Microparticles for Superefficient Protein Purification ........................................... 47
World‘s First Method for Continuous Purification of Valuable Antibodies ............ 49
Genome of the Chinese Hamster Deciphered ..................................................... 50
Green Chemistry for the Pharmaceutical Industry ................................................ 53
facts & figures .................................................................................................... 57
acib areas ........................................................................................................... 58
acib partners ....................................................................................................... 60
acib owners ........................................................................................................ 61
project design ..................................................................................................... 63index
5. 5
There is and will always be much to learn from nature. The Aus-
trian Centre of Industrial Biotechnology (acib) is a biotech rese-
arch institution with the vision to replace traditional industrial
technologies by new, more ecological and economic methods
and to find new beneficial products that are based on natural
processes. Therefor we connect the experience of 200+ highly
qualified employees at acib with the additional knowledge of
50+ key researchers and their research groups at our internati-
onal scientific partners to fulfill the needs of international bio-
tech, pharma and chemical companies.
Altogether, with 25+ years of experience in biotechnology acib is
a perfect research partner for change in industrial production –
focused on biocatalysis, industrially used cells, synthetic biology,
enzymes and (pharmaceutical) protein production and purifi-
cation. acib translates academic knowledge into new industrial
applications and products with higher values, lower costs and an
optimized environmental balance.
Our biotech stories show a part of our repertoire in the world of
biotechnology that we jointly developed with 150+ international
companies and scientific institutions within the acib network.
We are highly grateful to all partners who allowed us to create this brochure.
acib – Innovations from Nature
6. 6
HOST CELL & VECTOR ENGINEERING
Our expertise on bacteria, filamentous fungi, yeast, an-
imal (CHO) and human cells in combination with the
know-how in vector engineering allows us to address a
huge diversity of scientific and industrial needs and to
provide customized solutions for production or biologi-
cal plant protection.
PROTEIN CHARACTERISATION & OPTIMISATION
Our awarded „Catalophor System“ allows us to identify
unknown enzyme functions. The further characterisa-
tion of proteins and their functionality is the basis for
targeted engineering to provide tailor-made sulitions
meeting the needs of modern biotechnology.
NOVEL COMPOUNDS & REACTION CONDITIONS
Novel routes providing innovative alternatives for reac-
tions that are currently economically and/or ecologically
problematic – this key expertise of acib provides solu-
tions for critical steps in biocatalysis that can lead to
substances that could not be synthesized previously.
NOVEL ENZYMES
Our know-how in structural biology in combination
with innovations in bioinformatics to model the active
sites of enzymes as well as the expertise in synthetic
biology using non-canonical amino acids to modify
enzyme functionality offer innovative routes to novel
enzymes. New synthetic pathways with 10+ steps allow
us to produce highly valuable compounds biotechno-
logically.
DOWNSTREAM PROCESSING
The combination of expertise on bioseparation pro-
cesses with know-how on mathematical modelling and
analysis of biophysical properties of macromolecules is
the basis for the design of alternative approaches such
as continuous bioseparation as well as their prediction
and better understanding.
BIOINFORMATICS AND MODELING
Experts at acib provide solutions that use rational de-
sign to reduce the resources that need to be invested
into empirical approaches. acib methods facilitate the
development of optimised processes or the search for
new enzyme functionalities dramatically.
UPSTREAM PROCESSING
The integrated approach of monitoring, modelling and
fine tuning of bioprocesses – acibs expertise therein
helps to improve efficiency and reduce costs of biotech-
nological production processes and to design new pro-
duction strategies.
ANALYTICS
Besides a broad panel of standard methods and all
”omics-technologies” acib provides access to high-
end analytical tools established within the centre and
sophisticated instrumentation for chemical- and bio-
analysis which are operated by highly-trained employ-
ees.
About acib – Fields of Expertise
7. 7
statisticsandadvanceddatahandling
polymer & environmental bio-
technology
synthetic biology, synthetic
pathways
m
olecular, structural &
cell biology
directedevolution,site
directedmutagenesis
m
etabolite production
CHO technologies & human cell
lines
bacterial, yeast, fungal &
proteinexpressionsystems
fermentation&
bioprocessengineering
screening&isolationof
microorganisms
biopharmaceutical
technologies
biocatalysisin
organicsynthesis
reaction engineering &
process optimization
whole cellbiotransformation
assay developement, high through-
put screening
synthesis of enantiomeric
pure compounds
bioprospecting
&
biological plant
protection
genomics,metabolomics,
proteomics
metabolicmodeling,bioinformatics
new, greener
and more
economical
bioprocesses
for industrial
application
enzymeproduction,
purification&
immobilization
9. 9
According to the manufacturer Chanel, it’s most famous
perfume “No. 5” sums up for “secret opulence and im-
perishable femininity”. What does that have to do with
biotechnology? A lot, considering the Austrian Centre
of Industrial Biotechnology (acib). Many perfumes smell
particularly well because of an odorant from lily of the
valley. Unfortunately, this component is available in the
plants only in spring and in minute amounts. Using an
enzymatic approach, a team headed by Prof. Kurt Faber
(University of Graz and acib) was able to produce valuable
fragrances in highest purity for the first time.
The scientific challenge was to carry out the asymmetric
reduction of C = C bonds selectively and with high pu-
rity while gaining only one of two possible chiral prod-
ucts; in this case lysmeral/Lilial™. That is impossible using
classical chemical synthesis. Up to now, the odor had to
be obtained in poor yield directly from the plants. acib
researcher Clemens Stückler used biocatalysis, which is
based on environmentally friendly, enzymatic natural pro-
cesses that are adapted for industrial application.
During the past years, the asymmetric bioreduction of
alkenes (bearing an electron-withdrawing, activating
group) catalysed by enzymes/flavoproteins has emerged
as a highly valuable tool for the biocatalytic synthesis of
nonracemic – or – substituted aldehydes, ketones, car-
boxylic acids/esters, nitriles and nitroalkanes. Especially
the aldehydes are interesting compounds not only for fra-
grance industry. Thanks to the acib-method optimized by
Stückler it is now possible to produce the appropriately
selected chiral molecules in pure form.
This way, nonracemic aryl substituated -methyldihydro-
cinnamaldehyde derivatives employed as olfactory prin-
ciples in perfumes (Lilial™, Helional™) were obtained via
enzymatic reduction of the corresponding cinnamalde-
hyde precursor using cloned and overexpressed ene-re-
ductases. The product’s yield and quality are more than
satisfactory: The odorant used in many perfumes is avail-
able with a purity of 99%.
Ultimately, the research project won an Excellence Award
from the Austrian Federal Ministry for Science and Re-
search, which was awarded to Stückler for his PhD thesis
“Asymmetric Reduction of C = C bonds”. All results were
possible because of the cooperation of acib, the Universi-
ty of Graz and BASF as an industry partner. “acib provided
the enzymes which originate from tomatoes or brewer’s
yeast”, says the chemist Stückler, while University of Graz
assisted with infrastructure and additional knowledge.
BASF contributed financially to the research project.
Special aldehyde-based compounds are available with an ecofriendly note since researchers at
acib have mastered the asymmetric C = C reduction selectively and in high yield thanks to a se-
lected ene-reductase. As a result, important odorants are accessible in highest purity.
Homage to Coco Chanel
10. 10
“For effects and unwanted side effects read the patient
information leaflet ...” - every one of us is knowing a sen-
tence like this by heart from the days of our early child-
hood. A key technology for the investigation of effects
and unwanted side effects is subject of a research project
carried out by the Austrian Centre of Industrial Biotech-
nology (acib). Together with our industrial partners Novar-
tis and F. Hoffmann LaRoche the acib scientists have devel-
oped a technology, which enables to simulate in vitro the
metabolization of drugs in the human body - a “liver in a
test tube”. The liver is the primary organ for metaboliz-
ing pharmaceuticals; the test uses non-Cytochrome-P450
enzymes for the simulation of the metabolic processes in
the lab.
Pharmaceutical testing is required to ensure that the drug
is not only effective but ideally doesn’t produce unwant-
ed side effects, either. To date, pharmaceutical industry
needs to predict all possible breakdown products in the
body resulting from the use of the drug, produce them
chemically and test all of them for their effects. “At the
worst all predictions prove wrong because the metabolic
processes in the body don’t go off as expected”, explains
Margit Winkler, scientist at acib. The new acib method
uses endogenous enzymes and in vitro simulates the me-
tabolizing of the drugs in the body.
The pharmaceutical industries keep developing new drug
candidates to enhance the treatment possibilities of doc-
tors and thus improve our health. The question is: What
happens to pharmaceutical agents in the body? “On
the one hand the compounds bring about the de-
sired effects, on the other hand they are degrad-
ed so that they can be released more quickly”,
says project manager Winkler.
In addition to reductases/dehydrogenases
and hydrolases, to date five other oxida-
tive enzyme classes have been known
as possibly responsible for the first met-
abolic step: Cytochrome P450 enzymes
(CYPs), flavin monooxygenases (FMOs),
monoamine oxidases (MAOs), aldehyde
oxidase (AO) and xanthin oxidases (XO).
Which of those enzymes in the end degrades a special
agent depends on its chemical structure.
Together with F. Hoffmann LaRoche and Novartis acib-researchers developed a new key tech-
nology for the pharmaceutical industry: The first test system in a preparative scale simulating in
vitro the metabolization of drugs in the human body.
Liver in a Test Tube
as a New Pharma Key Technology
11. 11
Sandoz – effective together
WHEN PLEASURE
IN LIFE MEETS
PERFORMANCE
Remarkable developments at Sandoz are the result of effectively combining individual talents, personal interests and
professional qualifications. This is why we are looking for employees who are passionate about everything they do and
want to work with us towards our common goal: providing patients in Austria and around the world with high-quality
and affordable pharmaceutical products. Sandoz is one of the biggest pharmaceutical companies in Austria, employing
more than 4000 people in four locations. As part of the global Novartis Group, we develop, manufacture and market
patent-free pharmaceutical products – especially antibiotics, injectable cancer drugs and innovative biosimilars.
Join us!
Apply at www.sandoz.at/karriere
During the past years research has mainly concentrated on
the CYP family and comparably little attention has been
paid to the other four enzyme classes, the so-called non-
CYP metabolizing enzymes (NCMEs). In cooperation with
F. Hoffmann LaRoche and Novartis acib has now dedicat-
ed itself to these enzymes. “We intend to have available
each single enzyme from the human degradation metab-
olism in order to simulate special functions of the human
liver”, explains the acib scientist.
With this “artificial liver” enzyme set the pharmaceutical
industries are able to test new agents and know, at a very
early stage, which breakdown products are formed.
This information at hand - together with an abundance of
the right enzymes - makes it a child’s play to produce suf-
ficient quantities of the degradation products for further
investigations - no more guessing!
The acib method was successfully used for the degrada-
tion of moclobemide - a monoamine oxidase A (MAO-A)
inhibitor known under the brand names Aurorix or Maner-
ix prescribed to patients with depressions and is finally be-
ing used in drug development. Together with a processes
based on enzymes from almond trees and pig liver and
others acib can look back at a series of new processes for
the pharmaceutical industries.
13. Pine trees and red ants have something in common: Both
use alkaloids to banish enemies. These organic ingredi-
ents are more and more in demand because of their en-
vironmental friendliness and safety. The problem is that
they are only present in minimal amounts in natural form.
Chemical synthesis in turn is complicated and expensive.
Researchers at the Austrian Centre of Industrial Biotech-
nology (acib) and at the University of Graz led by Prof.
Wolfgang Kroutil have now developed a new key tech-
nology to produce a promising alkaloid variety much eas-
ier than ever using biocatalysis.
So remarkable the about half an inch wide pine weevil
is, so harmful it can be. The insects, which play dead at
the slightest vibration, live on young spruce or pine trees,
where they place their eggs into the stocks. Occurring in
large numbers, the critters can cause great harm, because
the infected trees are consistently condemned to death. “In
the northern hemisphere, this could be a real problem”,
says Prof. Kroutil. Natural alkaloids are perfect remedies,
which expel the beetles in a biological manner. The func-
tion of the alkaloid is similar to territorial marking of preda-
tors: If a newbie finds a marking scent, he knows that there
is already someone else in place and he stays clear of the
area. One of these alkaloids is “Dihydropinidine” which be-
longs to the class of 2,6-dialkylpiperidines. The substance
has a major drawback: In its natural form it is present only
in minute quantities in some pine varieties. Until now the
production of this substance in larger quantities has near-
ly been impossible, because up to 14 very sophisticated
chemical synthetic steps were necessary.
An acib-research group led by Prof. Kroutil found a new
approach to this class of substances. “The problem with
many syntheses is that you have to protect certain parts
of the parent molecule to get the desired reaction only at
a certain position”, explains the researcher.
Without protection, the result is an useless substance. For
chemists, this means many reaction steps until the desired
substance is eventually synthesized in minimal quantities.
The acib-researchers have found an enzyme, which re-
duces the number of steps from 14 to only 3. The first
and last steps of the synthesis are “chemical”, the cen-
tral one will be accomplished by a highly specific “omega
transaminase”. This enzyme yields the product avoid-
ing the undesired byproducts occurring in the chemical
approach. This saves time and energy and reduces the
use of environmentally harmful organic solvents. Thus
the new method is not only a step forward in the battle
against the beetle but opens up new opportunities in the
production of biologically highly active alkaloids.
Using the new synthesis technique, the chemical industry
can synthesize environmentally friendly products against
pests based on dialkylpiperidin including antifeedants as
that against the pine weevil but also agents against bacte-
ria (bactericids) or fungi (fungicides) that can be produced
on a commercial scale now. Just recently, the method has
been adapted for producing “Isosolenopsin”. The sub-
stance is an alkaloid oozed by red ants for defense. It is
interesting for industrial application because it has strong
antibacterial properties. In addition, it acts anti-hemolytic
(prevents the destruction of red blood cells) or anti-ne-
crotic (helps against the death of tissue).
The importance of the new concept developed within
the internal acib-partnership is proven by its publication
in “Angewandte Chemie”, goo.gl/4qD4dF. The method
was engineered in a research project with Sandoz.
13
Researchers from the Austrian Centre of Industrial Biotechnology shorten the production of bi-
ological agents from 14 to 3 steps. Eco-friendly products not only to cope with chewing pests,
bacteria or fungi can be produced easier and environmentally friendly.
„Pine Aroma“ Against Beetle Invasion
14. 14
BIOTECHNOLOGY, BIOREFINERY
AND SUSTAINABLE
PROCESS DEVELOPMENT
TU WIEN FOR SUSTAINABLE SYSTEMS AND HIGH WATER QUALITY
Modern technology of crop production requires reduced use of chemical pesticides and fertilizers as well as strict
toxicological regulations.
TU WIEN is conducting research on bioeffectors – viable microorganisms that directly or indirectly influence
plant health and thus may be used for the development of biofungicides and biofertilizers. We study the ecology,
physiology and genomics of natural microbial antagonists across various ecosystems and transfer the mecha-
nisms to biocontrol applications.
To control undesirable microbes and their toxic metabolites in water and food products TU WIEN is developing bio-
analytical methods for environmental monitoring based on contemporary DNA technologies and flash test systems.
Contact and Address:
TU Wien
Institute of Chemical Engineering
Director:
Univ. Prof. Dipl.-Ing. Dr. Anton Friedl
Tel. +43-1-58801-166200
anton.friedl@tuwien.ac.at
www.vt.tuwien.ac.at
Getreidemarkt 9/166
1060 Vienna Austria
BIOREFINERY AT TU WIEN
Institute of Chemical Engineering leads an interdisciplinary
competence platform on BIOREFINERY to produce high-
quality pharmaceutical and food products from agricultural
waste. Our aim is to expand chemical technology to the use
of raw materials in the development of innovative products:
BIOREFINERY process development and the implemen-
tation of a BIOREFINERY pilot plant to use agricultural waste
such as raw cellulose substrates, C5 and C6 sugars and
lignin fractions.
BIOREFINERY product development through enginee-
red microorganisms producing high-quality, fine chemicals
for food, energy and pharmaceutical industries. Examples
the production of the sugar replacer erythritol directly from
wheat straw, screening for novel enzymes and genetic
improvement of enzyme producing fungal cell factories.
BIOREFINERY analytics as a structural and quantitative
monitoring of raw materials for optimum control of the
chemical and/or enzymatic degradation of raw materials.
FUNGI AS A BIOTECHNOLOGY TOOL
TU WIEN is developing genetically engineered microbes for
industrial needs. We do rational design of proteins and invent
molecular tools for their recombinant production in fila-
mentous fungi, yeasts and bacteria. We study regulation of
gene expression, design producing strains and construct
of whole-cell biocatalysts. For example, our mutant strains
can produce valuable medical compounds from abundant
biopolymer chitin. Genomes of other fungi are modified for
production of enzymes for biofuels and other industries.
Technology no longer merely targets machines and
instruments, but extends to life itself! TU WIEN is intensely
engaged in research on biotechnology and in underlying
fundamental disciplines such as microbiology and ge-
netics. We have expertise in gene technology, systems
biology,syntheticbiologyandmicrobialbiodiversityaswellas
reactor engineering and downstream technologies.
15. 15
Carbon dioxide is the best known greenhouse gas. Since
the introduction of CO2
pollution allowances, carbon dio-
xide is a dreaded thing for the industry. For scientists at
the Austrian Centre of Industrial Biotechnology (acib) und
the University of Graz the exhaust has a new meaning:
they have developed a way to use CO2
as a raw material
for chemical synthesis – an important step forward in the
face of global climate change and dwindling resources.
Researchers around Silvia Glück and Prof. Kurt Faber use
the carbon in CO2
for the synthesis of valuable chemicals.
The reaction is carried out using modified decarboxylases
as biocatalysts. The acib-researchers used phenolic com-
pounds as output material, but pyroles and indoles also
can be used as a substrate.
The resulting aromatic carboxylic acids have a huge im-
portance for industrial application: Salicylic acid, a pre-
cursor of aspirin, was synthesized in this way as well
as p-aminosalicylic acid, an active ingredient for the
treatment of tuberculosis. Depending on the kind of
enzyme, highly specific substances are accessible – even
those who were not synthesizable with classical chem-
ical methods – like compounds gained via asymmetric
hydration.
Currently the acib-researchers optimize the enzymatic
process to improve the specifity and selectivity of the re-
action and to broaden the spectrum of substrates and
reaction products.
Another advantage of the enzymatic approach: The
classical method (Kolbe-Schmitt reaction) is not only
non-specific – it causes unwanted side products – it also
requires a high energy input (high temperatures and pres-
sures). The highly specific enzymatic variant operates at
room conditions and meets environmental and economic
requirements of a modern synthesis technology. The en-
vironmentally friendly process eventually opened up new
possibilities in building innovative compounds for the
pharmaceutical, cosmetics and chemical industries.
The project was honored at the 2013 Houska-Prize,
Austria’s most prestigious award for scientific progres.
An enzymatic approach allows the use of carbon dioxide CO2
as a raw material for chemical syn-
thesis. With the help of decarboxylases, industrially most interesting molecules can be produced
“climate friendly” and highly specific.
Greenhouse Gas CO2
as a Resource
17. 17
Whether in salads, for frying fish or meat or just as a
snack on white bread - for millennia olive oil has been
one of the tastiest natural products. And it is one of the
healthiest because of the high content of unsaturated
fatty acids and additional substances, which are pres-
ent in minute amounts in olives (and in virgin olive oil
“extra virgine”). A particularly valuable one is 3-hydroxy-
tyrosol. “The substance is said to protect the cells and
thus delays aging and prevents various diseases”, says
Margit Winkler, researcher at the Austrian Centre of In-
dustrial Biotechnology (acib). This is due to the antioxi-
dant effect, which is even stronger than that of ascorbic
acid, the well-known antioxidant Vitamin C from citrus
fruits.
No wonder that the substance is always in demand as
a natural food supplement or as a component for cos-
metics. The crux of the matter is the availability of
3-hydroxytyrosol: olive trees grow in limited geograph-
ic areas where olives can be harvested once a year and
should remain a valuable and tasty food and not become
the raw material for a substance that is present only in
minimal amounts. As to Winkler, the separation is diffi-
cult and expensive.
A research group of acib and the Swiss industrial partner
Lonza has found a way to produce the valuable substance
biotechnologically. A patent has been filed and the proj-
ect outcomes were scientifically published. The biotech-
nological route uses bacteria (Escherichia coli) as a cell
factory. The researchers have integrated a new enzyme
from another microorganism (called Nocardia), which is
able to convert a cheap, low-carbon acid (3,4-Dihydroxy-
phenylacetic acid, DOPAC) into the valuable 3-hydroxyty-
rosol. The entire reaction was improved so that the cofac-
tors otherwise necessary for this complicated conversion
are no longer needed - the high art of biotechnology.
“Fed with DOPAC at laboratory scale there is a turnover
of 100 percent using our modified Escherichia coli cell
factories”, explains acib-scientist Winkler. What works in
the lab could be upscaled into industrial mesures.
ANTIOXIDANTS AND CANCER
Oxidative stress damages living cells. They form very ac-
tive “radicals”, which react with everything that comes
their way. This causes cancer or an even faster cell death.
For example, skin cells exposed to UV light show such
oxidative stress. The skin ages faster, dries out, becomes
wrinkled. In the worst case, skin cancer is the long-term
consequence. Antioxidants neutralize the free radicals
and decrease the risk of damages dramatically. 3-hy-
droxytyrosol has already been tested in many studies and
showed “cytoprotective effect”: Protection of cells was
shown with intestinal and brain cells, cells of the cardio-
vascular system, liver and various other cell types. For the
authors of the studies, 3-hydroxytyrosol can prevent can-
cer, is anti-inflammatory and has a positive effect on the
cardiovascular system.
The results were finally published in “ChemCatChem”:
goo.gl/vogdYl
Protection against cellular aging in a natural way: Austrian researchers biotechnologically pro-
duce a valuable antioxidant from olives that is more effective than Vitamin C. It can prevent
cancer and has many positive effects on human health.
Cell Aging Delayed
19. 19
The Austrian Centre of Industrial Biotechnology (acib)
uses the positive aspects of synthetic biology for the ecof-
riendly production of a natural compound. The challenge
of the biotechnologists Tamara Wriessnegger and Harald
Pichler in Graz was to produce Nootkatone in large quan-
tities. The substance is expensive (more than 4000 USD
per kilogram) and can be found only in minute quantities
in grapefruits. At the same time the need is great, be-
cause Nootkatone is used as a high quality, natural fla-
voring substance in millions of liters of soft and lifestyle
drinks, as a biopharmaceutical component or as a natural
insect repellent.
FOUR NEW GENES
“We have installed new genetic information in the yeast
Pichia pastoris, so that our cells are able to produce
Nootkatone from sugar”, says acib researcher Tamara
Wriessnegger. The genome of the yeast cells has been
extended with four foreign genes derived from the cress
Arabidopsis thaliana, the Egyptian henbane Hyoscyamus
muticus, the Nootka cypress Xanthocyparis nootkat-
ensis and from baker’s yeast Saccharomyces cerevisiae.
Ultimately, the genetic information of the aroma found
in one grapefruit leads to millions of liters of tasty juice.
With the help of the new genes the yeast is capable to
synthesize the high-prized, natural flavor (more than
4000 euros per kilogram) in a cheap way and in useful
quantities from sugar (one euro per kilogram).
Nootkatone is an important substance for the food, phar-
maceutical and chemical industries, says Harald Pichler.
As an insecticide it is effective against ticks, mosqui-
toes or bedbugs. In the medical field, the substance has
shown activity against cancer cell lines. In cosmetics, peo-
ple appreciate the good smell, in soft drinks a fine, subtle
taste. Because the natural sources by far cannot meet the
demands, the acib method replaces chemical synthesis -
an energy-consuming and anything but environmentally
friendly process. The common biotech variant via Valen-
cene and a chemical synthesis step is less ecofriendly,
more difficult and expensive. Pichler: “With our method,
the important and expensive terpenoid Nootkatone can
be produced industrially in an environmentally friendly,
economical and resource-saving way in useful quanti-
ties.”
SYNTHETIC BIOLOGY
Synthetic biology could be of vital importance to human-
ity, as Artemisinin shows. Thanks to this substance ma-
laria is curable. Unfortunately, it could be found only in
tiny quantities in the sweet wormwood – until the US re-
searcher Jay Keasling was able to transfer the appropriate
production route from the plant in bacteria. With these
“synthetic” organisms the active ingredient is produced
at lower costs.
The acib research results were published in the journal
“Metabolic Engineering”: goo.gl/xu2s0h
New method allows production of expensive grapefruit aroma Nootkatone biotechnologically
from cheap sugar using a “turbo-yeast”. The versatile, healthy and tasty substance is used in
drinks, pharmaceutical products or even as an insect repellent.
Millions of Liters of Juice
from One Grapefruit
20. 20
“Fuel instead of food”, is currently a common question -
although this need not be. The first generation of biofuels
is mostly made of corn, wheat or sugarcane. But that’s
not exactly the ideal solution. Biofuels of the 2nd gener-
ation are made of agricultural waste – from wood chips,
straw or specially cultivated “energy crops”. The Austri-
an competence centre acib (Austrian Centre of Industrial
Biotechnology) has found ways to make these renewable
sugar resources available for industry and for the produc-
tion of biofuels.
The enzymes that are used are called cellulases. They can
cleave cellulose and hemicellulose - both components of
wood (besides lignin) – into small sugar molecules, ex-
plains Professor Christian Kubicek (Technical University
of Vienna). In the framework of the center of excellence
acib, he worked together with researchers in Graz and
at an industrial partner’s site on the access of new in-
dustrial sugars from renewable resources. “The enzymes
work like choppers”, says Professor Anton Glieder, key
researcher at acib, “the long cellulose chains are trans-
ported through the enzymes. Thereby, the enzyme cuts
small sugar molecules off the comparatively huge cel-
lulose chain, until the whole cellulose is digested into
smaller sugars.” The best enzymes for the process are
produced using the fungus Trichoderma reesei, which
normally grows on decaying wood residues. In the Styrian
project “MacroFun” at Graz University of Technology the
fungal enzymes were improved by using the yeast Pichia
pastoris to make the “molecular shredder” more robust,
declares Glieder.
Admittedly, the general procedure is still extensive, says
Kubicek. The plant remains or “energy crops” such as
flower stalk grass (Miscanthus) or switchgrass (Panicum
virgatum) must first be “unlocked” to separate the lignin
and make the cellulose accessible. Then specially designed
cellulases come into play and cleave the long cellulose
chains into small sugars. These are finally converted –
similar to the alcoholic fermentation in wine – from yeast
to bioethanol, which can then be used for biofuels. The
great advantage of this method: food remains completely
unaffected and the carbon footprint looks a lot better.
How promising this type of sugar and subsequently bio-
fuel production is, shows the fact that alone in Europe
400 million tons of wheat straw per year accumulate. To
ensure a sustainable use, 30% of them remain on the
field to regenerate the soil, but the enormous residue can
be processed further. Actually, about 1 liter of bioethanol
could be made from 5 kg of straw. The goal for acib is to
raise the yield by optimization of the degrading enzymes
and to make more yet unused sugar sources available
for biofuel production. 2nd
generation biofuels are more
or less ready to use.
Today wheat or corn is mostly used to produce biofuels. But this misuse of food is not necessary
at all. acib and an industrial partner developed methods, which use agricultural waste and straw
as basis for new biofuel materials.
Advanced Biofuels Without Food Use
22. 22
Wood floors, garden furniture, paintings in various indoor
and outdoor use – hardly anyone uses paints in the course
of her or his life. Most commonly in use are so-called “
alkyd resins”; in Europe alone there are produced 700,000
tons per year. But hardly anyone was aware until now
that the paint will dry, because the heavy metal cobalt
accelerates the drying process. Recently it was discovered
that cobalt is potentially carcinogenic which makes the
paint industry think on alternatives.
Cytec Austria and the Austrian Centre of Industrial Bio-
technology (acib) found a solution to replace Cobalt by
enzymes which make paints ecologically friendly. “We
had the idea to use enzymes instead of metals in 2009”,
says Professor George Gubitz, enzyme specialist at acib
and professor at the Institute for Environmental Biotech-
nology at the University of Natural Resources and Life
Sciences Vienna. The enzyme was derived from the tree
sponge Trametes hirsute or “Hairy Bracket”, isolated
from Gubitz’s garden in Graz. “We knew that the fungus
contains the enzyme type we were looking for”, explains
Gubitz. So a piece of mushroom was harvested, the
active enzyme isolated and proliferated.
The enzyme called “Laccase” is able to combine fatty
acid molecules in the alkyd resin with the aid of oxygen
from the air so that the paint dries and solidifies. Previ-
ously this was only possible with the help of heavy metals;
particularly cobalt was used. Lately a new EU-regulation
demands that only 10 ppm of cobalt are allowed in new
in coatings as of 2013. Currently, a useful paint works
only with a significantly higher amount of the potentially
harmful substance!
The paint manufacturer Cytec Austria with laboratories in
Graz and the production unit in Werndorf is a pioneer in
environmentally friendly technologies. The development
of water-soluble resins and varnishes in the end of the
20th century was a major contribution to the banning of
toxic and hazardous solvents from these products.
Now Cytec goes a step further and eliminates the next
health hazard by replacing cobalt by biocatalysts. “The
attributes “free of heavy metals” and “biocatalyzed”
are perfect marketing arguments for the sale of new
products”, states project manager Roland Feola from
Cytec Austria.
In the project partnership Cytec Austria provides the alkyd
resin while acib handles the enzymes and provides the
scientific basis specifically in the area of biotechnology.
Besides Cytec handles the application-oriented issues of
the paint manufacturing process and brings in it’s know-
how about product- and market requirements.
The partnership finally led not only to a more environ-
mentally friendly paint, but also to a new measure-
ment method for monitoring the hardening of the resin.
“We have developed an optical measurement system
to monitor the decrease of the oxygen content in the
coating film”, says acib-scientist Katrin Greimel. Oxygen
decreases during the hardening process. This
is the first high-precision observation method of paint hard-
ening in a supersmall scale which facilitates research a lot.
The project has been filed for a patent. Because of a
shared knowledge business model, acib is open for fur-
ther cooperations In specific painting applications.
Austrian scientists banish toxic heavy-metal catalysts from paints. For the first time pollutants
are replaced by natural enzymes. The project has been knighted scientifically: on the front page
of the journal “Green Chemistry”.
Enzymes from Austria Revolutionize
the World of Paints
23. 23
ABOUT ALKYD RESINS
Alkyd paints consist of fatty acid molecules, color pigments and “siccatives” (the dryer). When a handyman
spreads the paint on the furniture, the siccatives accelerate the connection of the fatty acid molecules by the
incorporation of atmospheric oxygen and thus the drying of the paint. Previously, this task was taken over by
metal compounds based on cobalt which turned out to be potentially harmful. Now it is possible to replace
cobalt by enzymes – by natural and environmentally friendly biocatalysts.
24. 24
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25. 25
Industry produces 250 million tons of plastics per year; for
packaging, clothing, decoration and much more. A good
part of it is not utilized in a savvy way. In Europe, only a
third of 14 million tons of textile waste per year are used
for recycling. The rest is burned, processed into low-grade
plastics or ends up in the environment, where industrially
produced plastic hardly rots. Huge plastic islands diving in
the oceans for decades testify about that.
This problem could be solved. Biotechnology, with the
help of microorganisms or enzymes, it is possible to de-
grade polymers into their building blocks - under envi-
ronmentally friendly conditions, without the addition of
chemicals or energy. acib scientists led by Prof. Georg
Gübitz (University of Natural Resources and Life Scienc-
es and acib) do research on biological recycling for many
years. Meanwhile four patents are pending. The acib
technology is based on the adaption of natural enzymes
with the ability of cleaving polymers similar to their nat-
ural substrates. “Naturally occurring cutins are akin to
synthetic polyesters according to their bonds and water
repellent properties. That is why cutinases also can dis-
mantle plastics into their original molecules”, explains
Gübitz. Using targeted mutagenesis the biotechnologists
have optimized cutinases so that they can better degrade
synthetic polyesters. The enzymatic degradation works
with PE (polyethylene terephthalate) as well es PU (poly-
urethane). More plastics are under investigation.
Because nowadays many plastics are composite products,
this way it is possible to selectively dissolve the desired
molecules from plastic waste. Gübitz: “With the help
of the enzymes we are obtaining the starting molecules
from various plastics in high purity.”
For waste treatment, no longer used plastics have to be
cleaned, crushed and finally broken down using spe-
cifically enzymes. “Our process has the advantage that
plastic waste no longer needs to be further sorted”, says
acib-researcher Enrique Herrero-Acreo.
The acib research not only deals with the degradation of
polymers, but also with their modification and the cre-
ation of bio-plastics that are degradable in nature. “We
use enzymes to alter the surfaces of plastics specifically
and gently. We think of manufacturing durable mem-
branes, which are both breathable and anti-static”, ex-
plains biotechnologist Gübitz.
When talking about decomposition of synthetic mate-
rial, Gübitz draws a comparison with wood: “This bio-
polymer is very durable with proper care, but in nature
it rots in a few years.” As micro plastic and other hardly
degradable polymers are known to pollute the terrestrial
aquatic systems massively, acib researchers Doris Ribitsch
and Karolina Härnvall are investigating whether and how
plastics are being degraded in aqueous systems such as
rivers or lakes. Conclusions about the microbial and enzy-
matic degradation allow the design of new plastics that
are broken down in an aquatic environment into harmless
substances and not longer burden the environment as
those hardly degradable plastic islands that have formed
in the oceans.
The project won the Austrian Neptun Award 2015, which
is donated by the Austrian Federal Ministry of Agriculture,
Forestry, Environment and Water Management once in
two years.
Every year huge amounts of plastic are globally converted into minor valued materials, ending
up in the waste incineration or pollute the environment; for example in the form of floating
garbage islands. Researchers at acib have found ways to disassemble old plastic into valuable
starting molecules and develop new bioplastics, which are fully degradable in nature.
New Value for Old Plastics
27. 27
As high-precision miniature tools from nature, enzymes
can solve certain tasks perfectly. The search for new indus-
trial usable enzyme functions is very complex. A project
of the Austrian Centre of Industrial Biotechnology (acib)
and the University of Graz opens up a new approach: The
“Catalophor System” – a combination of database and
search engine – filters desired enzyme functions out of
tens of thousands of protein structure data and can even
track functionalities that have not been discovered yet.
The procedure is similar to a typical search engine type
search, although the input of data is a bit more com-
plicated. All starts with the question for the required
enzyme function. “We focus on the active site of the
enzyme sought-after and write a program which specifies
the positions and distances of the most important amino
acids as well as important structural features in the vicin-
ity of the active site”, explains acib researcher Christian
Gruber.
On the basis of this script the “Catalophor System”
browses 110.000+ database entries for similarities. The
result is a weighted list of possible candidates. In the
next step the most promising candidates are manufac-
tured and tested in the lab. The preliminary work on the
computer saves countless experiments and screenings for
new enzyme functionality.
The database itself is constantly being expanded. “Every
week about 150 new structures are added,” says Georg
Steinkellner from acib. “We also refine the entire system
to answer more complex search queries.”
The “Catalophor System” has a high practical benefit for
science and industry. “Based on the protein structures we
can discover new possible reaction pathways of enzymes
that have not been described yet. For the chemical in-
dustry our approach opens up new reaction pathways
that were not possible until now”, says Prof. K. Gruber.
The opportunity to replace conventional industrial pro-
cesses with environmentally friendly and more economic
enzymatic methods increases. And it can offer alter-
natives to patented industrial enzymes.
The method was applied for a patent and published in
“Nature Communications” (goo.gl/eK3HAJ) and finally
won an Innovation Award for process development at the
CPhI 2014 – the world’s largest fair for the pharmaceutical
and chemical industries.
A new search engine, including a database with more than 100.000 proteins, opens up new
possibilities in the search for industrial usable enzymes or for alternatives to patented biocata-
lysts. The method was published in Nature Communications.
“Enzyme-Google”
Reveals Hidden Possibilities of Nature
28. 28
Sugar is not the same as sugar. Sucrose, the white sub-
stance which we use to sweeten or for cooking, is just
one example of a variety of sugar compounds that have
a special meaning in nature; for example in the form of
cellulose as a stabilizing structure for plants. Or as a pre-
biotic oligosaccharide in mother’s milk, which helps that
a baby’s intestinal flora can develop perfectly. The EU
research project SUSY deals with producing particularly
valuable sugars more easily. The starting material is our
retail sugar – sucrose.
The tools used for modification of glycosides are three
enzymes – highly specific instruments in micro format:
Sucrose synthase turns sucrose into an activated sugar. A
glycosyltranferase transmits the activated sugar onto an
industrially desired molecule. The overall objective is to
produce a new, effective sugar compound. “Finally fruc-
tan sucrase makes the process more diverse”, explains
acib researcher Christiane Luley, “because other activated
sugars are accessible that can be transferred to specific
target molecules”.
For industry, the resulting bioactive molecules are very
interesting, the scientist explains: “We are able to syn-
thesize compounds that occur in nature only in minute
amounts. They could be used as improved UV protection
in cosmetics. There is just as much potential at classic
sugar substitutes with a high sweetening intensity – but
without calories or tooth-damaging properties – as with
new sugar substances that are even effective against can-
cer.” The antioxidant potential of the new sugar mole-
cules makes them ideal preservatives, which increase the
storability of food – all based on the concepts of nature.
The EU-funded project SUSY deals with improving these
three enzymes, manufacturing them in large quantities
and finally optimizing the biochemical conversions. The
EU-subsidized total budget until the project ending in
August 2017 is five million euro. 800,000 euro will be
turned over at acib in Graz, the rest from seven other
project partners in Austria (TU Graz), Germany, Spain,
Belgium and the Netherlands. The acib is responsible for
the process development for industrial enzyme produc-
tion of large quantities.
HEALTHY OLIGOSACCHARIDES
Sugar chemistry is a speciality of acib and Graz University
of Technology (TU Graz). Since more and more studies
show that breast milk is supporting babys health more
than milk substitutes, research attempts to investigate
the benefits of breast milk ingredients. More than 100
oligosaccharides are described to have highest effective-
ness, eg in brain development or in binding pathogens in
the intestinal tract. The complex production of these mol-
ecules is best achieved enzymatically. For example with
a sialyltransferase that was modified by researchers led
by Prof. Bernd Nidetzky (TU Graz and CSO acib) in order
to be able to synthesize two important oligosaccharides
from human milk in useful amounts. Normally, sialyltrans-
ferase transfers a sialylic acid group from CPM-N-acetyl-
neuraminic acid to various saccharides with a terminal
galactosyl group (like lactose). “In the original reaction, a
2,3-link is formed whereas in our modified reaction a 2,6-
link comes about”, explains Nidetzky. Both products are
found in human milk, but have different characteristics.
Actually researchers from acib and TU Graz are develop-
ing and modifying more enzymes for glycosylation and
the production of valuable oligosaccharide molecules oc-
curring in human milk.
Sweetening power , UV protection, sugars against spoilage of food or even for cancer protection –
EU research partnership about the power of sugar relies on knowledge of the Austrian Centre of
Industrial Biotechnology (acib) in glycoside chemistry.
The Sugar Side of Biotechnology
29. 29
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Defense strategies are not only important in chess or
military tactics but also in nature. Especially plants are
masters in this discipline. Some stone fruit, almond trees
or even ferns defend their young buds against feeding
pests with cyanide. The poison expels the greatest enemy.
This is due to an enzyme called hydroxynitrile lyase (HNL),
which can release molecularly stored hydrogen cyanide.
What is useful for the plants, is also in demand in industry
where the reverse reaction of the HNL-enzymes allows
to bind cyanide to different molecules. This creates a
double benefit. On the one hand, it is possible to recycle
unwanted cyanide wastes, which for example are gener-
ated during the production of acrylonitrile. Acrylonitrile is
not only used in adhesives, it is also the raw material for
polyacrylonitrile or “acrylic”, an important fiber for tex-
tiles. On the other hand, industry gains valuable building
blocks for pharmaceutical agents or the vitamin synthesis.
The extremely high specificity of the HNL-enzymes makes
them so useful for industrial application. Ideally, through
biocatalysis valuable products are derived from inexpen-
sive precursors.
HNL-enzymes have a fine tradition in industry. The first
HNL enzymes have been successfully developed in the
mid-1990s at Graz University of Technology (TU Graz)
and were used industrially for the production of insect
repellents. Important improvements in the synthesis of
high-value products aroused more industrial interest. The
early enzymes certainly can’t meet all of today’s require-
ments, so researchers are searching for new HNL biocat-
alysts. Within the framework of the EU project KYROBIO,
which deals with production technologies for new mole-
cules, acib-researchers have successfully looked for those
bio-tools.
SMELL ENZYME ACTIVITY
The acib-researchers Margit Winkler, Elisa Lanfranchi and
Anton Glieder finally made a find in the white rabbit’s
foot fern, where the scientists sniffed enzyme activity.
“When you rub a young fern croizer between the fingers,
it smells of hydrocyanic acid and benzaldehyde (similar
to marzipan), indicating that there is enzyme activity”,
explains Margit Winkler, “knowing that ferns show the
desired activity, we have been searching in the woods
and in commercially available plants”. In three and a half
years the acib-researchers in Graz have kept a close eye
on eligible enzymes, examined their structure, produced
the biocatalysts biotechnologically and tested their activi-
ty. Finally, the enzymes of a commercial rabbit’s-foot fern
from the hardware store were the most promising. The
Styrian bracken fern also showed activity and is currently
being studied in more detail.
The new enzyme has an extremely high activity, although
it is not even optimized. “Our new HNL is more efficient
and simpler to handle than those previously used, be-
cause it is a small, uncomplicated enzyme”, says Anton
Glieder (TU Graz, acib). These results are a perfect basis
for the industrial utilization. The range of applications is
huge: It includes everything from crop protection to the
production of repellents against mosquitoes and Co.
The acib-method used for bioprospecting of enzyme
activities was published in the “Current Biotechnology”
Against voracious beetles or caterpillars plants protect themselves with cyanide. Certain en-
zymes release the toxic substance when the plant is chewed. These HNL-called enzymes are also
important for industry. acib found a new biocatalyst in a fern which outshines all other HNL-type
enzymes on the market.
Plant Defense as a Biotech Tool
32. 32
While more and more antibiotics are less effective and
bacteria develop unimagined resisting forces, the phar-
maceutical industry is in demand for alternative sub-
stances. Substances based on pyrrolopyrimidine seem to
be promising, because these chemicals can suppress the
genome synthesis in microorganisms by inhibiting certain
enzymes. This could be an interesting opportunity to fight
against resistant microorganisms. A new, high tempera-
ture resistant nitrile reductase discovered and modified
at acib is able to generate new pyrrolopyrimidine based
molecules to meet these requirements.
The research project about new nitrile reductases is a big
step for acib and a big step for organic synthesis, since
acib researcher Birgit Wilding has managed to reduce a
nitrile to an amine for the first time using a high-tem-
perature enzyme. The reaction step is frequently used in
organic synthesis and is in a classical manner only feasible
with considerable effort compared to the smooth enzy-
matic approach. But that’s not all – acib’s enzyme has a
number of advantages.
“We have used an enzyme from Geobacillus kaustoph-
ilus”, explains the acib researcher. G. kaustophilus is a
thermophilic microorganism, which is found in hot en-
vironments. Its enzymes are therefore particularly resis-
tant to heat. Knowing the coding sequence of the nitrile
reductase, the genetic information was transferred to
Escherichia coli – the standard production bacteria in
biotechnology. Because of its resistance to high tempera-
tures up to 65 °C, the purification is highly facilitated:
Using heat and ultrasound allows the separation in high
purity; without complicated cleaning processes. Active
site mutagenesis enhanced the enzyme potential.
Another advantage is the wide range of applications for
this nitrile reductase. It converts those nitriles particularly
well, which are in turn starting materials for compounds
with activity against bacteria and even tumors cells. The
enzyme may therefore be a key to new drugs or substi-
tutes for no longer effective antibiotics. Research expects
a lot especially from pyrrolopyrimidines - with this class of
substances, acib’s enzyme is good deal.
Finally, the enzyme from G. kaustophilus functions with
a broad substrate range and a higher transformation rate
than known from nitrile reductases. “We have already
tested 22 major substrates, but not all can be converted
satisfactorily. If there is interest, we could easily improve
the enzyme so that it meets the requirements of the phar-
maceutical and chemical industry”, explains Birgit Wilding.
The project was published in the scientific journal
“Advanced Synthesis and Catalysis”: goo.gl/SRtThT
acib researchers created a temperature resistant nitrile reductase for organic synthesis. The
enzymes converts pyrrolopyrimidines at temperatures up to 65 °C and can be adapted to specific
substrates to meet industrial requirements.
High-Temperature Reductase
for Organic Synthesis Available
33. 33
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35. 35
Transaminases are not only indispensable for prokaryote
and eukaryote metabolism; they can also be used for
synthesizing precursors of active pharmaceutical ingredi-
ents more environmentally friendly and more specifically
compared to the classical chemistry. The mechanism pro-
vided by transaminases is important for example in the
large scale synthesis of amino acids or chiral amines that
finally simplify the production of drugs for AIDS therapy,
knows Katrin Weinhandl, researcher at the Austrian Cen-
tre of Biotechnology (acib). A project of acib and a com-
pany partner deals with the production of transaminases
in a large scale. acib has facilitated the manufacturing
process of the enzymes essentially by developing a new
test. It allows determining whether the biotechnologi-
cal production has led to useful transaminases of a high
quality or not.
Transaminases are important enzymes in every organism;
they are used in the metabolism of proteins. Since the
pharmaceutical industry searches for more environmen-
tally friendly and efficient production methods for active
ingredients, biocatalysts are highly asked industrial tools.
This also applies to transaminases - in this case branched
chain aminotransferases - which transfer the amino groups
from one molecule to another; more specifically, efficient-
ly and ecologically compared to chemical synthesis.
Together with a company partner acib investigated a way
to produce transaminases in large quantities, so that this
type of enzyme can be used efficiently in the industri-
al production. “We use a transaminase originating from
E. coli bacteria, which is finally produced harnessing the
yeast Pichia pastoris. Our experiments showed that only
Pichia can handle the required enzyme quantities”, ex-
plains Katrin Weinhandl. To determine whether enough
active transaminases are present after biotechnological
production - or to identify optimal production clones -,
acib researchers developed a colorimetric test that visu-
alizes the activity of transaminases and makes it measur-
able. The new assay couples the transaminase reaction
with two other enzyme reactions. An enzyme from the
Styrian horseradish catalyzes the last step: A peroxidase
that finally leads to a green color, if the transaminase ac-
tivity is sufficient.
Green light for the new assay was given in the form of a
publication in the “Tetrahedron” journal: goo.gl/NCVJjg
Biocatalysts are being increasingly used in manufacturing of pharmaceuticals. While supporting
the upscaling of the production of transaminases, acib researchers developed a method to quan-
tify enzyme activity. The test is based on a color reaction that is catalyzed by an enzyme from
horseradish.
Styrian Horse Radish
Visualizes Active Enzymes
36. 36
The fungi (Rhizoctonia solani) is stealthy blight, infesting
beets or corn at their roots and becoming visible only
shortly before the harvest. The fungal rot begins early
in the season, working its way from the inside out, and
only becoming visible in the fall, destroying the possibility
of a harvest. Year after year crop failures due to attacks
by pests and pathogens are reported in the media de-
spite their being treated with pesticides. Crop failure is
further exacerbated by pesticide treatments which cause
the death of insects such as bees through neonicotinoids.
“There are also more extreme environmental conditions
such as periods of hot weather, drought or flood disas-
ters, to be taken into account when considering the ex-
tent of damage caused by pesticide use alone”, states
acib researcher Christin Zachow.
The Austrian Centre of Industrial Biotechnology (acib) is
perfecting protective methods which will make the use of
“chemical mace” measures obsolete. One such research
project currently underway involves biological plant pro-
tection, in which microorganisms (bacteria) work as body-
guards for the safeguarding of seeds like corn, canola,
tomato, sorghum, or sugar beet. The underlying principle
is that special bacteria are planted in combination with
the plant seeds in fields. Together with Graz University of
Technology and five international industry partners, acib
engages the growth promoting properties of microorgan-
isms: While the seed germinates, the microorganisms are
simultaneously developing and supplying the plant with
nutrients, promoting growth, warding off pests, reducing
the stress on the crop and increasing their resilience.
STRESSED CROPS
“Crops are challenged by climate change, drought, and
high salted floors. These nutrient deficiencies occur as a
result of monoculture practices”, states Christin Zachow.
Since 2011, she has been managing project research and
delivery in collaboration with Prof. Gabriele Berg - a pi-
oneer in this research field - from the Institute for En-
vironmental Biotechnology at Graz University of Tech-
nology. Their primary task has been to find bacteria that
are adapted to extreme environmental conditions. Every
plant needs specific bacteria, and every soil type harbors
specific bacteria. For example, researchers who work in
the areas of moss and lichen research have found that the
Naturally occurring bacteria as a crop protection agent are now available for use in crop protec-
tion to alleviate the contamination of soil with pesticides - arguably the most environmentally
friendly way of plant protection developed to date.
Bodyguards for Precious Seeds
37. 37
former tolerate acidic pH values and nutrient deficiencies,
while the latter accept UV-light and drought.
Bacteria that promote growth are identified, character-
ized and tested for their resistance to stress. Zachow: “We
want to know which genes are activated by which par-
ticular environmental conditions in order to ensure that
the bacteria will be ideally matched with crops under the
local conditions.” When a promising population of bac-
teria is found, it is deliberately improved by researchers
so that the “microbiome” will have an optimal outcome
under their given environmental conditions. Success has
been recorded with the bacterial species Pseudomonas
poae and Stenotrophomonas rhizophila. While Stenotro-
phomonas caused an enormous burst of growth of crops
in the salty steppe of Uzbekistan (300 % more than with-
out microbiome treatment), Pseudomonas made a simi-
larly positive impact in the sugar beet test field from acib’s
industry partner in Germany. Five international, industrial
enterprises are currently involved in the research project.
HEALTHY DIET
After finalizing the preliminary investigations, target
bacteria have come into interaction with their prospec-
tive host plants. Zachow: “Plants are searching for ex-
actly those types of bacteria that they need for perfect
growth.” The bacteria-host-interaction is similar to that
which occurs in the human intestine, in which a specific
microflora is beneficial to human health. The culmination
of the research and development of a commercial prod-
uct has led to a bacterial-seed-combination. In moist soil
types, the bacteria grow along with the germinating seed
and at the same time protect it.
Our goal: “We strive to develop plants with optimal
health to provide consumers with an optimal basis for a
healthy diet”, says the scientist, “a functioning biologi-
cal plant protection system offers a viable alternative to
pesticides.”
Biological plant protection is undeniably a significant step
towards ensuring a biologically sound agricultural indus-
try producing healthier food.
Ultimately, the acib method is in competition with con-
ventional systems of pesticide driven “plant protection”.
The chemical industry turns over about 40 billion euros
a year in chemical plant protection products worldwide,
and a third of these chemicals ends up on the fields in the
EU alone. There is a lot of money to be made using bio-
logical plant protection when more and more customers
call for healthier food.
38. The natural, frequently occurring mycotoxins in grains
such as corn, rye, wheat or barley are not only a natu-
ral danger for chickens, cattle and pigs which eat con-
taminated feed grains. Certain types of these poisons
- around 300 are currently known - can even reach the
consumers of milk, meat or eggs. Just think of ergot,
which repeatedly lead to deaths until the 20th century. It
is no wonder then that the Food & Agriculture Organiza-
tion FAO classifies the contamination with mycotoxins as
a main threat to humans and animals. FAO estimates that
a total of around a quarter of the world’s food production
contains mycotoxins. This fact, however, wouldn’t have
to be a threat.
The precautionary treating of animal feed with enzymes
that can break down this natural fungal toxins complete-
ly and without residues, plays an important role in the
quest for a healthy animal feed - and thus also for food
security for consumers. The Lower Austrian company
BIOMIN can fall back on many years of experience in the
use of enzymes against various fungal toxins. Dieter Moll,
research group leader at the Biomin Research Center in
Tulln: “Although we use the enzymes in a very gentle way
to produce valuable feed, they are highly effective and
efficient in fighting against pollutants. Since the toxins
are completely eliminated by these enzymes, they can
no longer exert their toxic effect.” The removal of tox-
ins happens in the digestive tract of animals, where the
feed admixed enzymes have full effect against fumonisin,
deoxynivalenol or zearalenone. On the other hand, afal-
toxins are being removed by binding to clay minerals in
the feed mixture.
For the production of enzymes Biomin utilizes the yeast
Pichia pastoris, which is routinely used in biotechnolo-
gy. “Yeast can not only ferment wine or soften dough,
special varieties can also produce enzymes that are of a
high industrial interest. Like the biocatalysts that are used
to inactivate fungal toxins”, explains project leader Prof.
Diethard Mattanovich (University of Natural Resources
and Life Sciences Vienna (BOKU) and head of “Systems
Biology & Microbial Cell Factories” at acib). The scien-
tists at acib, Biomin and BOKU finally developed a yeast
strain, which allows producing these enzymes quickly and
in large quantities. In addition, the production organism
has been adapted to the technical requirements and the
process paths were optimized to produce the enzymes as
cost-effective as possible. The project finally was awarded
with an Austrian Science2Business Award in 2013.
Mycotoxins in animal feed should be no longer a prob-
lem - however, the technology already exists. And it is
improved in Austria. “Our cooperation continues. We are
optimizing the production system in order to expand it to
other enzymes”, says Mattanovich. The goal is to be able
to degrade enzymatically as many mycotoxins as possible.
Fungal toxins in animal feed are regularly causing troubles in the food industry. Nevertheless
extremely poisonous mycotoxins in feed grain must not be a problem. Within the acib-consor-
tium, a method for the industrial production of enzymes has been developed, which can degrade
fungal toxins. Thus, the feed is safe - and our food as well.
Enzymes Against Fungal Toxins
in Animal Feed
38
40. Swine fever is one of the world’s most dangerous ani-
mal diseases and was previously difficult to control. The
international research network of the Austrian Centre
of Industrial Biotechnology (acib) demonstrates how
(harmless) parts of a dangerous virus can be transformed
into something very useful. Scientists at the Universities
of Innsbruck, Salzburg and the University of Natural Re-
sources and Life Sciences Vienna and the company part-
ners Sandoz and Boehringer Ingelheim revealed the mys-
tery of the enzyme “Npro” after eight years of research.
The autoprotease plays a major role in infection by the
swine fever virus.
The research team led by Prof. Bernhard Auer (Universi-
ty of Innsbruck) successfully deciphered the structure of
the enzyme. Knowing the 3-dimensional shape of the en-
zyme, it was possible to understand the method of the
virus for attacking its targets. This is the basis for new
methods to control the infection and to combat the virus.
Biotechnologically more important are the enzyme’s special
properties. The extraordinary abilities of Npro - to from in-
clusion bodies and to split itself off from the viral protein –
makes it an ideal vehicle for the biotechnological pro-
duction of therapeutic proteins or other valuable protein
based substances. Using Npro for the formation of fusion
proteins cumulated in inclusion bodies simplifies the bac-
terial protein production and purification extremely.
“The method can be improved and adapted to new phar-
maceutical needs”, explains Auer, “resulting in higher
quality medicines, which can be produced cheaper”.
This project is yet another example of how joint research
at acib leads to new technologies and competitive advan-
tages for the company partners in the acib partnership.
The per se harmless enzyme “Npro” plays a major role during the attack of the swine fever vi-
rus. Nevertheless, the enzyme can be used perfectly for manufacturing medical drugs. The acib
research network revealed its secrets and thus not only opened up new possibilities for the pro-
duction of protein drugs, but also for controlling the virus.
Virus in the Service of Health
40
ABOUT NPRO
The comparable small enzyme Npro has the extraordinary ability to cleave itself of from an attached protein.
In the biotechnological production using Escherichia coli as a cell factory, this is quite convenient, because the
bacteria not only produce the desired macromolecule, but also hundreds of other proteins from which the de-
sired product must be separated without any residue. Causing E. coli to synthesize the desired protein coupled
to Npro as a fusion protein, all becomes easier. Npro then forms inclusion bodies, small definite structures in
the microorganism in which the product is concentrated. The inclusion bodies are easier to separate from the
rest. Because of Npro’s ability to split itself off subsequently, biotech industry saves a lot of effort during the
purification process. acib’s industrial partners have access to this smart process already.
42. 42
The air we breathe contains much more information than
how many drinks you had at the last party. You can even
draw conclusions about a person’s state of health. In hu-
mans, thanks to the most sensitive analytical instruments,
even cancer signals can be found in the breath. A ciga-
rette leaves signs in the exhaled air a week after smoking.
Not only people, but also microorganisms “breathe”.
After several years of joint research of acib and the Ty-
rolean business partner Ionicon on the “breath” of mi-
croorganisms, the sensitive analysis of the components
of respiratory air has become possible. For the first time
the health status of bacteria or yeasts, which are grown
in a fermentation vessel to produce active agents for the
pharmaceutical industry can be observed in real-time.
“Our analysis method detects individual substances
which are directly related to the metabolism of the cell,”
explains Gerald Striedner, acib-project leader at the Uni-
versity of Life Sciences Vienna (BOKU). With this infor-
mation, process engineers can quickly intervene in the
production process if something does not go according
to plan. Preventing an overuse of the cells, it is at the
same time possible to avoid too few or inferior products.
“The challenge was to develop a technology that meets
the strict requirements of the pharmaceutical industry
and at the same time leads the “breath” to the analyser”
as unchanged as possible”, says Rene Gutmann from
acib-partner Ionicon. The analyzing unit – a highly sen-
sitive proton transfer mass spectrometer – must be con-
nected to the sterile production vessel without any chance
for infections. In addition, the information conveyed in
the exhaust must reach the analyzer unchanged to en-
able reliable conclusions. To this end, the researchers in
the acib-network developed a suitable interface between
fermenter and analyzing unit. For the first time the anal-
ysis of industrial fermentation processes in a production
scale of several 1000 liters is possible without interfering
with the sterile areas.
The safety in manufacturing active pharmaceutical ingre-
dients rises while costs decrease because production loss-
es can be prevented and the processes can be improved
immediately – based on the statements of the on-line
analysis of the cell metabolism. Previously, for process
control technicians had to draw samples, work them up
und finally analyze them – in comparison a slow and cost-
ly method. “Our new technology once again highlights
the innovation performance of Austrian biotechnology”,
says Mathias Drexler, director of acib. The innovation
has been awarded the Vienna INiTS Award 2012 in the
category “Life Science”. The award was handed over to
acib-researcher Markus Luchner for enabling the “trial
and error” method in fermentation processes to be re-
placed by a substantial on-line analysis.
A new method allows analyzing the exhaust of those microorganisms in real time, which
produce active agents for the pharmaceutical industry. This facilitates process control.
Transparent Bioprocesses by Analyzing
the Respiratory Air of Microorganisms
ABOUT PTR-MS
The PTR-MS method can detect dozens of volatile products that are “exhaled” by microorganisms during fer-
mentation, including acetone, acetaldehyde, indole, isoprene, ethanol or methanol. If Escherichia coli (in the
biotech industry most widely used species of bacteria) “exhales”, for example, tiny traces of acetaldehyde in
a fermentation that is an indication that the desired sugar breakdown no longer takes place (along with the
production of the target product), but the microorganisms have changed to an unwanted metabolic pathway
(a kind of acid fermentation). On the basis of the results of the air analysis, the process can be redirected.
43. 43
Manifold expression and
production strategies
Record-breaking
productivities
MeOH-induced and
MeOH-free processes
Pichia pastoris
Protein Expression
Excellence
www.vtu-technology.com
Tailor-made glycoproteins –
VTU Pichia boosting
Pichia GlycoSwitch®
44. 44
Yeast is being used by mankind for longer time than any
other microorganism. Bread, beer, wine - all of these could
not be produced without Saccharomyces cerevisiae (bak-
er’s yeast) and other yeast species. Over the last decades
yeast has become indispensable for industrial biotechnol-
ogy as a reliable cell factory. Valuable products ranging
from enzymes to active pharmaceutical ingredients are in-
dustrially produced using yeast, mostly by a species called
Pichia pastoris that is particularly productive.
Because of its long and varied utilization, yeast is one of
the best studied organisms. Besides its industrial applica-
tion Pichia pastoris is also used by scientists as a model
organism for studying cell structures. Everything seemed
familiar – until this year. Researchers of the Austrian Cen-
tre of Industrial Biotechnology (acib) and the University
of Natural Resources and Life Sciences Vienna (BOKU)
have elucidated a new pathway that makes the yeast Pi-
chia pastoris unique. “We were able to show that the
assumptions and models that have been used in the last
30 years are not right”, explains Prof. Diethard Matta-
novich (BOKU and head of the research area “Systems
Biology & Microbial Cell Factories” at acib).
The new pathway explains the utilization of methanol as
“feed”. Yeasts such as Pichia pastoris belong to the rare
kind of microorganisms that are able to utilize this sim-
ple alcohol as nutrient. Mattanovich: “The cells use that
option, for example, when they grow naturally in the sap
of trees, where methanol is present.”
The researchers around project leader Dr. Brigitte Gasser
discovered amazing similarities with plants. These use
carbon dioxide (CO2) as a nutrient and recycle the green-
house gas in cell organelles called chloroplasts. Eventual-
ly CO2 is converted to biomass. Pichia works similarly: It
converts methanol, which consists of one carbon atom
like CO2, in a cell organelle called peroxisome. The de-
cisive role in both processes is the formation of chemical
bonds between carbon atoms and the rearrangement
into sugar molecules and other substances, which are
necessary for the synthesis of biomass. “So far we did
not know where these rearrangements are performed in
the cells, and which genes control them”, says Brigitte
Gasser.
Just as little was known about the genetic encoding of
this metabolism. Most cells have one gene available per
protein and metabolic step. Pichia is evolutionarily on
the safe side. All genes for methanol manipulation are
duplicated, as Mattanovich and Gasser have discovered
together with 13 scientists who were involved in this
research project. The genes do not only have an addition-
al genetic information so that the appropriate reactions
are located to the peroxisome. They are active only when
methanol is present as a nutrient source.
Duplicate copies of genes safeguard survival of the biotech yeast Pichia when only methanol is
present as feed. A recently elucidated metabolism is similar to that used by plants for the utiliza-
tion of CO2
. Metabolic models of last decades are wrong.
Newly Discovered Metabolism Certifies
Evolutionary Advantage for Yeast
45. 45
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lower cost than currently established production processes. Therefore we combine the latest
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For these findings, the researchers have re-evaluated the
entire data, which have emerged in the recent years while
improving Pichia pastoris biotechnologically at acib and
BOKU. “The interpretation of our systems biology data
revolutionized the understanding of cell biology,” says
Brigitte Gasser, delighted about the new knowledge
of life processes on earth. The work was recently pub-
lished in the prestigious journal BMC Biology. The results
demonstrate the leading role of Vienna researchers when
it comes to the biotech yeast Pichia pastoris.
The work was recently published in the journal “BMC Bi-
ology”: goo.gl/BYZZeR
The results demonstrate the leading role of Vienna
researchers when it comes to the biotech yeast Pichia
pastoris.
47. 47
Seven of the ten best-selling drugs in 2012 were biophar-
maceuticals; biotechnology in pharmaceutical production
is still growing. A severe problem is the cleaning of prod-
ucts; up to 80% of the total production costs are spent
for protein purification. The Austrian Centre of Industrial
Biotechnology (ACIB) has developed a method based on
microparticles, which reduces five purification steps to
only one; a revolution in the cleaning process of biophar-
maceuticals.
“Our micro-particle system comprises a new cleaning
method especially for proteins for medical application,
which are produced by microorganisms. Using our micro-
particles, the manufacturing process of biopharmaceu-
ticals becomes qualitatively better and faster”, explains
Prof. Bernd Nidetzky, CSO of acib. The new process was
developed within a cooperation of acib and Boehringer
Ingelheim RCV.
“FIVE IN ONE”
“The economic relevance of this new purification method
lies in its simplicity and speed. We aggregated five pro-
cess steps into a single one”, says Georg Klima, head of
Process Development Biopharma at Boehringer Ingelheim
in Vienna, “in addition, we expect an even better quali-
ty because the microparticles directly absorb the product
out of the cells with high specifity.” A key issue was the
transfer of technology from a research level into corporate
laboratories, which was completed within a few weeks.
Today most medicines are produced biotechnologically. A new cleaning method developed at
acib combines five purification steps and leads to an extremely facilitated, more economical and
ecological manufacturing process.
Microparticles for Superefficient
Protein Purification
ABOUT THE MICROPARTICLE TECHNOLOGY
Currently, chromatography is used for standard-
ized protein purification. Industry fights with
slow binding rates, clogged or damaged mate-
rial, product losses and other obstacles.The new
acib system works differently: Scientists prepared
charged microparticles based on the ion exchange
principle with a size of one to two microns. The
entire binding operation is completed within 30
seconds. Additionally, a continuous process based
on the micro particle technology has been estab-
lished to further accelerate the biopharmaceutical
purification.
48. 48
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49. 49
Imagine a loved relative suffering from cancer – and you
could not afford a treatment because the drugs are too
expensive. The Austrian Centre of Industrial Biotechnolo-
gy (acib) developed a method with the power to reduce
production costs of highly valued drugs significantly.
Without antibodies we would be at the mercy of patho-
gens or cancer cells. Therapeutic antibodies are used
as passive vaccines, for cancer treatment or for con-
trolling autoimmune diseases such as multiple sclerosis.
According to “bccresearch.com”, the global market for
antibody drugs was worth 70 billion USD in 2014 and
should rise to 122 billion USD until 2019.
Two thirds of those molecules are produced biotechno-
logically using Chinese hamster ovary cells (CHO cells).
Actually the major cost factor for industry is purification
using “protein A” affinity chromatography where tens
of thousands of liters of culture volume have to be pro-
cessed annually. About 80 % of the production costs fall
upon purification.
Here the new purification method comes into play.
Researchers from the acib and the University of Life
Sciences Vienna developed the first downstream pro-
cessing method for recombinant antibodies from clari-
fied CHO cultures. A feasibility study exemplified by the
purification of immune globulin G (IgG) shows that the
method can compete with “protein A” affinity chromatog-
raphy in terms of yield and outperforms chromatography
according to the speed of operation. A further advan-
tage is the transferability of the operation parameters
from the actually used batch to the continuous approach.
“Our method shows great potential as a new plat-
form technology for the pharmaceutical industry”, says
Prof. Alois Jungbauer, who is in negotiations with sev-
eral international companies about building pilot plants
based on acib’s technology.
The purification method was published in the “Biotech-
nology Journal”: goo.gl/KYvWLD
An external scientific comment emphasizes the relevance
of the project: goo.gl/q89aAt
Scientists at acib develop world’s first continuous purification method for valuable drugs. This
will lead to significantly reduced production costs and to cheaper pharmaceuticals that are
affordable for non-privileged health care systems.
World‘s First Method for Continuous
Purification of Valuable Antibodies
50. 50
The Chinese hamster ovary cells (CHO cells) are an in-
dispensable part of modern medicine, because they are
the most sought after vehicles for production in phar-
maceutical industry. A group of researchers led by Prof.
Nicole Borth has decrypted the genome of the Chinese
hamster – a result of the research partnership between
the Austrian Centre of Industrial Biotechnology (acib), the
University of Natural Resources and Life Sciences and the
University of Bielefeld (CeBiTec). “We now understand
better how the cells function and can adjust them to the
desired requirements”, explains the scientist and thinks
not only of new biopharmaceuticals and treatments but
also of cheaper medicines that are affordable ideally even
in underprivileged countries.
Because the hamster genome is comparable in its size
to the human one, it was necessary to cope with huge
amounts of data. “We produced 1.4 billion short segments
of DNA”, says Karina Brinkrolf. She was responsible for
sequencing at CeBiTec. The challenge was to assemble
these parts like a puzzle to get the entire genome, which
is spread over 11 pairs of chromosomes.
Whether antibodies, blood clotting factors, rheumatism
therapy or anti-cancer drugs – the pharmaceutical indus-
try brings more and more therapeutic proteins on the
market. Unfortunately, agents in human medicine are
not knit in a simple pattern. There are chemically sim-
ple varieties, consisting of single molecules with a few
atoms. Therapeutic proteins, however, are complex struc-
tures made up of hundreds of amino acids. In contrast
to the simple products, these proteins must be perfectly
adapted to the human organism, so that no secondary or
defensive reactions can happen.
“Since 1987 the most common production vehicle for
these substances have been artificially cultured Chinese
hamster ovary cells”, says Nicole Borth. The first active
agent produced this way was a drug administered to
heart attack patients to stimulate the dissolution of blood
clots. Actually 70% of the active pharmaceutical ingredi-
ents are produced via CHO cells. Hamsters need not die
for this anymore, because industry and researchers repro-
duce the cells that were once isolated in 1957.
Because ovarian cells of the Chinese hamster are the most popular vehicles for making valu-
able therapeutics, the genome decrypted within the Austrian Centre of Industrial Biotechnology
(acib) enables developing of cheaper, more effective therapies.
Genome of the Chinese Hamster
Deciphered
51. 51
™™™Ǥƒ–‘ŽŽǦ„‹‘Ǥ…‘
”‡ƒ…‡† Š”‘ƒ–‘‰”ƒ’Š› ‘Ž—•
The in vitro cultivation, however, leads to difficulties:
“These cells are subjected to natural changes over time”,
says researcher Borth, “the activity of genes is different in
all laboratories that develop and grow hamster cells. The
original genetic material is subject to constant modifica-
tion.” This is an advantage - considering the adaptabili-
ty of cells - and a disadvantage, because it may happen
that, for the specific purpose, important elements of the
genetic material have mutated. The sequenced genome
of the “original hamster” is the perfect reference to ex-
amine and adapt the genetic material of the production
cells.
To enable access to the data for as many researchers as
possible the scientist has founded the online platform
www.chogenome.org together with two colleagues
where a lot of work material regarding the Chinese ham-
ster ovary cells is available. Nicole Borths vision: “We can
produce agents more efficiently and cheaper – at prices
that any average health system can afford; ideally even in
Third World countries.”
The research results were published in August 2013 in the
journal “Nature Biotechnology”: goo.gl/yAI82I
53. 53
Producing medical drugs is a resource-devouring matter.
“For one kilogram of a active pharmaceutical ingredi-
ent (API) in a traditional production processes industry is
consuming typically 100 or more kilos of raw materials”,
explains Anton Glieder, professor for biotechnology at
Graz University of Technology and key researcher at the
Austrian Centre of Industrial Biotechnology (acib). Not
to mention the use of energy. In addition, the processes
consume a lot of time and cause harmful waste that has
to be eliminated. In addition, the pharmaceutical industry
has to cope with limited and expensive resources. Plati-
num for example, a commonly used high-value catalyst, is
becoming increasingly rare and expensive. Overall, green,
environmentally friendly alternatives are required.
Pharmaceutical industry is looking after these alterna-
tives within the EU project CHEM21 - Chemistry for the
21st Century. In cooperation with scientific partners in
England, Germany, Belgium and the Netherlands, acib
has prevailed in the competition for this project and is
since 2012 working with the pharmaceutical companies
GSK, Pfizer, Sanofi, Bayer, Orion, Johnson Johnson and
several SMEs on new, “green” production processes. The
acib’s contribution is based on the experience in biocatal-
ysis and especially in synthetic biology. “Our main focus
is the development of tools for environmentally friendly
multistep syntheses that enable microorganisms to pro-
duce APIs in a consistent high quality instead of dirty and
unspecific chemical methods”, explains acib researcher
Birgit Wiltschi.
At half-time of the project, promising achievements were
visible. The acib-scientists have succeeded in producing
simultaneously several interesting substances such as car-
otene with yeast cells. The carrots’ colour is a result of
intracellular built carotene. Additionally, the substance is
a precursor of vitamin A. For this purpose it was necessary
to stably incorporate four bacterial genes in Pichia pasto-
ris, the most important yeast strain for biotech industry.
“It is our vision to incorporate new genes in a way that
our cells master a new pathway and are able to produce
quality products from simple sugars. Products that occur
in nature only in tiniest quantities or have to be synthe-
sized complicated and absolutely not environmentally
friendly”, says Martina Geier, yeast-specialist the acib.
The main task is to establish new pathways based on up
to 20 foreign genes in bacteria or yeast, so that the mi-
croorganisms are capable of producing valuable products
for human medicine in complex cascade reactions. The
researchers have already installed nine foreign genes suc-
cessfully and thus were able to synthesize carotene from
sugar as well as the antibiotic violacein. The patented
techniques, which are developed for installing the new
genes, can be utilized by the pharmaceutical industry to
manufacture important products - like new antibiotics
against resistant bacteria or substances for cancer therapy.
Active ingredients in drugs (APIs) are a billion dollar busi-
ness. More than 120 billion has been implemented world-
wide in 2014 - a growth rate of around 7 percept per year.
In the 26 million Euro IMI EU project CHEM21 23 partners including acib are developing more
environmentally friendly methods for industrial production of active pharmaceutical ingredients.
The goal: Modifying microorganisms such that they are using new metabolic pathways and thus
can produce important substances reliably, environmentally friendly and in a high quality.
Green Chemistry for the
Pharmaceutical Industry
