A multi functional enzyme with several catalytic domains

1. Keshav Raj Bhusal
University of Oslo
Faculty of mathematics and natural science
Department of bioscience

2. Biological process catalysed by FAS
FATTY ACID SYNTHESIS

3. Fatty acid synthesis - overview
Functional /Catalytic domains of
FAS complex
ACP = acyl carrier protein
AT = acetyl transferase
KS = ketoacyl synthase
MPT = malonyl/ palmitoyl
transferase
KR = ketoreductase
DH = dehydratase
ER = enoyl reductase

4. Class of Fatty acid synthase
Fatty acid synthase
Type I Type II
● huge multifunctional
protein
● fungi and mammals
● mono functional
proteins(dissociated)
● Bacteria and plants

5. Type I FAS -Fungal
Catalytic domains are distributed over two non-identical polypeptide
chains

6. Overall architecture of the fungal FAS
height =260A ° width = 230A °
●barrel shaped with
equatorial ring
(wheel), and dome
shaped apical rings
●KS and KR domain
found in equatorial
ring
●MPT departs
directly from the
wheel and lead to ER.
● AT, DH, along with
ER form apical ring

7. The central wheel
●Equatorial region of a
complex resembles a
wheel like structure
●Two domains KS and KR
forms outer circular frame(3
each domains arranged in
alternating fashion)
●central hub is built from
tightly packed 6 alpha
helices
● spoke radiates from hub
and connects KS and KR
domains

8. Distribution of the  and chains
●alpha subunit which
contains KS and KR
domains forms central
wheel
●beta subunit that contains
AT, DH, ER forms apical
rings

9. The reaction chamber
●Central wheel divides
complex into two reaction
chambers.
●Each reaction chamber has
3 full set of catalytic
domains.
●ACP is attached to two
ancher points A1, and A2.
● Domains of each sets are
arranged around the anchor
point A1 in the reaction
order.

10. Summary
 Fungal FAS is barrel shaped(central wheel and two arms).
 Central wheel divides complex into two reaction chamber.
 Catalytic domains are distributed over two polypeptide
chains.
  chain forms central wheel
  chains form arms.

11. Fungal FAS Vs mammalian FAS
(A short comparison)
Fungal FAS Mammalian FAS
66-heterododecamer
2.6 megadalton
2homodimer
0.54 megadalton

12. Mammalian
Malonyl-CoA/Acetyl CoA trasacylase
(MAT)
Transfer of both substrates
Fungal
●Acetyl transferase (AT)
transfer of Acetyl CoA
●Malonyl/palmitoyl trasferase(MPT)
transfer of Malonyl CoA

13. Fungal
Mammalian
All catalytic domains are distributed over single polypeptide chain.

14. Fungal Mammalian

15. Conclusion
 FAS catalyses synthesis of fatty acids .
 Two types- type I and II
 Animals and fungi posses Type I FAS that integrate all
steps of fatty acid biosynthesis into complex assemblies
 Bacteria and plant posses Type II FAS with dissociated
enzymes.
 Architectural structure differs within type I FAS.

16. References
Jenni, Simon, et al. "Architecture of a fungal fatty acid synthase at 5 Å
resolution." Science 311.5765 (2006): 1263-1267.
Leibundgut, Marc, et al. "The multienzyme architecture of eukaryotic fatty
acid synthases." Current opinion in structural biology 18.6 (2008): 714-725.
Maier, Timm, Marc Leibundgut, and Nenad Ban. "The crystal structure of a
mammalian fatty acid synthase." Science 321.5894 (2008): 1315-1322.
Maier, Timm, Simon Jenni, and Nenad Ban. "Architecture of mammalian
fatty acid synthase at 4.5 Å resolution." Science 311.5765 (2006): 1258-1262.