Molecular basis for chlorizidine A biosynthesis. (a) Gene organization of the clz biosynthetic cluster from Streptomyces sp. CNH-287. See Table S1 for proposed function assignments. (b) Proposed polyketide biosynthesis of chlorizidine A (1). The conversion of 4 to the Clz6 AT-2 substrate 8 is proposed to involve a divergent FAS pathway (blue) via the FabF ketosynthase Clz11 and primary FAS reducing enzymes encoded elsewhere in the genome. Compounds 5a and 7a correspond to the free carboxylic acid of intermediates 5 and 7, respectively. Abbreviations: ACP, acyl carrier protein; AT, acyl transferase; CoA, coenzyme A; DH, dehydratase; ER, enoyl reductase; KR, ketoreductase; KS, ketoacyl synthase; R, thioester reductase.