Figure 1. The docking of ketosynthase (KS) and upstream acyl
carrier protein (ACP) domains within a modular polyketide synthase
(PKS). The Pikromycin precursor, Narbonolide, is biosynthesized through
the actions of 23 enzymatic domains and 7 ACP domains. As each ACP
carries out its reaction cycle, it docks and undocks each of its cognate
enzymes. The final reaction in the reaction cycle of the first 6 modules
in the Pikromycin PKS is transacylation, where an upstream ACP presents
intermediates to KS and only the fully processed species is permitted
onto its reactive cysteine. These checkpoints are exemplified by
PikMod6, in which PikACP6 and PikKS6 associate to enable the
transacylation of the hexaketide intermediate reduced by PikKR6.
KSQ, generates propionyl priming units; AT,
acyltransferase; KR, ketoreductase; KR0, epimerase;
DH, dehydratase; ER, enoylreductase; TE, thioesterase; unlabeled
circles, ACPs; unlabeled half-circles, docking domains.