The polyketide backbone of thiolactomycin is assembled by an unusual iterative polyketide synthase

Abstract

Following the in vivo investigation of thiotetronate assembly in Lentzea sp. and in S. thiolactonus NRRL 15439 (Havemann et al., Chem. Commun., 2017, DOI: 10.1039/c6cc09933e), the minimal set of genes required for thiolactomycin production was determined through heterologous expression and the mechanism for polyketide assembly was established in vitro through incubation of recombinant TlmB with its substrates in the presence of either nonhydrolysable or hydrolysable chemical probes. The results presented here constitute unequivocal evidence of enzymatic processing by an unusual iterative polyketide synthase.