Substrate Specificity in Ketosynthase Domains from trans-AT Polyketide Synthases

摘要

Type I modular polyketide synthases (PKSs) catalyze the production of a remarkable array of biologically active natural products, with many employed as antibiotics, immunosuppressants, anti-parasitics, and anti-tumor agents. Each PKS module possesses the enzymatic machinery for a single cycle of chain elongation and modification. Within a module, the acyltransferase domain (AT) loads an acyl-CoA derivative onto the phosphopantetheinyl (PPant) chain of the acyl carrier protein (ACP). Claisen thioester condensation, catalyzed by the ketosynthase (KS) domain, then results in chain elongation. The extent of P-keto processing is dictated by the presence of ketoreductase (KR), dehydratase (DH), and enoylreductase (ER) domains allowing production of hy-droxyl, olefinic, and fully saturated intermediates.