Fig. 4. Mechanism of polyketide chain extension in a prototypical module N. The ACP from the upstream module N – 1 transfers the intermediate to KSn in a process known as transacylation. ATn selects the appropriate extender unit and charges ACPn. Then, KSn catalyzes a decarboxylative Claisen-like condensation of the intermediate onto the ACPn-bound extender unit. The new ACPn-bound intermediate can then be processed by the domains of the reductive loop. The depicted module N harbors only a KR domain in the reductive loop, but DH or ER domains may also be present. The ACPn-bound intermediate is then ready to be transferred to either the downstream module N + 1 for another round of extension or to the C-terminal TE domain for offloading if module N is the final extension module of the assembly line.
