FabG: from a core to circumstantial catalyst
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Core biochemical pathways such as Fatty-acid synthesis II (FAS II) is ascribed to the synthesis of fatty-acids, biotin and lipoic acid in prokaryotes. It has two dehydrogenases namely, FabG and FabI which interact with the fatty-acid chain bound to Acyl-carrier protein (ACP), a well-studied enzyme which binds to substrates of varying lengths. This protein–protein interaction ‘broadens’ the active site of these dehydrogenases thus, contributing to their flexible nature. This property is exploited for catalysing numerous chiral synthons, alkanes, long-chain alcohols and secondary metabolites in industries especially with FabG. FASI relegates FASII in eukaryotes making it a ‘relic gene pool’ and an antibacterial drug target with diverse inhibitor and substrate markush. FabG often substitutes other dehydrogenases for producing secondary metabolites in nature. This redundancy is probably due to gene duplication or addition events possibly making FabG, a progenitor to some of the complex short-chain dehydrogenases used in organisms and industries today.
KeywordsBiopolymer synthesis Dehydrogenase Drug target Fatty-acid synthase (FAS) Ketoreductase Polyketide synthase (PKS)
Dr. Santanu Datta helped in conceiving the thought process for this study. Special thanks to Prof. Ramaswamy S., Dr. Nainesh Katagihallimath, Dr. Nagakumar Bharatham and Arindam Ghatak for introducing the structural and industrial aspects of these enzymes. Thanks to Prof. Sudip Kundu for helping me pursue this in an academic setup.
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