Fatty acid synthase

A multi functional enzyme with several catalytic domains

1. Fatty Acid Synthase (Type I-Structure and Function) 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  2 homodimer 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.