Figure 8.

Carrier proteins orchestrate the biosynthesis of a variety of metabolic products, including polyketides, fatty acids, and nonribosomal peptides.A–C, ACPs facilitate the extension and transfer of malonyl-based building blocks and intermediates in PKSs and FASs to manufacture polyketides or fatty acids, respectively. D, PCPs play a similar role in NRPSs but use amino acid building blocks to build peptide-based products. A, in type II PKSs, ACPs interact with a suite of enzymatic partners including MAT, KSCLF, ARO, CYC-TE, and KR domains. B, in type II FASs, ACPs interact with MAT, KS, KR, enoyl reductase (ER), dehydratase (DH), and TE domains, among others. C, in type I PKSs, megasynthases are made up of multiple (n) modules, and each module contains several catalytic domains. At a minimum, modules include an ACP, KS, and AT. D, similarly, type I NRPSs are multimodular systems with each module harboring at least a PCP, adenylation (A), and condensation (C) domain. The diversity of molecules produced by these systems is highlighted by showing the structures of actinorhodin and doxorubicin (type II polyketides), palmitic acid (fatty acid), erythromycin (type I polyketide), and enniatin (nonribosomal peptide). ACP, acyl carrier protein; ARO, aromatase; CYC, cyclase; FAS, fatty acid synthase; KR, ketoreductase; KS, ketosynthase; KSCLF, ketosynthase chain length factor; MAT, malonyl-CoA:ACP transacylase; NRPS, nonribosomal peptide synthetase; PCP, peptidyl carrier protein; PKS, polyketide synthase; TE, thioesterase.