Engineered biosynthesis of novel polyketides from Streptomyces spore pigment polyketide synthases

A series of 12 recombinants expressing sets of polyketide synthase (PKS) genes from the whiE (Streptomyces coelicolor), sch (S. halstedii), and cur (S. curacoi) spore pigment biosynthetic gene clusters were prepared and shown to produce four groups of novel polyketides. Mixtures of undecaketides and dodecaketides were produced by the minimal PKS alone (TW93b, TW93c, and TW93d) or in the presence of the (unnatural) act ketoreductase (KR) (TW94b, TW94c, and TW94d), whereas when the whiE-ORFVI cyclase was present, only dodecaketides (TW95a and TW95b) arose, in high yield. This implies that the whiE minimal PKS requires an additional subunit (the cyclase) to stabilize the complex between the long nascent polyketide chain and the minimal PKS to ensure that the chain reaches the full 24 carbons. These experiments suggest that the native spore pigment is a C24 molecule with a pentacenequinone structure which is first cyclized C9 to C14. A fourth set of uncharacterized polyketides was produced when the complete s...