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Structural insight into the substrate-shuttling mechanism of fatty acid synthase in yeast

29 June 2010. Fatty acid synthase (FAS) is the key enzyme for the biosynthesis of fatty acids in living organisms. The FAS in yeast belongs to the fungal type I family and has a total molecular mass of 2.6 MDa. Yeast has developed a rigid cage-like FAS machinery with six reaction chambers for the increased efficiency of fatty acid synthesis. In a recent paper published in the Proceedings of the National Academy of the USA Werner Kühlbrandt and colleagues present a 5.9-Å three-dimensional map of yeast FAS obtained by cryo-EM of single particles. The map shows considerable differences in domain organization compared to the four previously available x-ray structures, revealing significant conformational flexibility in the barrel wall. The acyl carrier protein (ACP) is found in several alternative locations next to the catalytic domains within the reaction chamber, providing direct evidence for a substrate-shuttling mechanism. The ACP is proposed to be the only mobile domain performing the substrate shuttling, unlike the open mammalian FAS structure with two reaction chambers where the efficiency of the fatty acid synthesis is determined by the high conformational flexibility of the complex.  More ...


Gipson P, Mills DJ, Wouts R, Grininger M, Vonck J, Kühlbrandt W (2010) Direct structural insight into the substrate-shuttling mechanism of yeast fatty acid synthase by electron cryomicroscopy. P Natl Acad Sci USA 107:9164-9.