Quartromicin Biosynthesis: Two Alternative Polyketide Chains Produced by One Polyketide Synthase Assembly Line

The antiviral compounds quartromicins represent unique members of a family of spirotetronate natural products. In this study, a biosynthetic gene cluster of quartromicins was identified by degenerate primer PCR amplification of specific genes involved in the biosynthesis of the tetronate moiety. The biochemical results confirmed that 1,3-bisphosphoglycerate was incorporated into the tetronate ring, and the intermediates of this ring were also reconstructed in vitro. The data also suggested a module skipping strategy for the production of two alternative polyketide chains by the same polyketide synthase assembly line. These findings set the stage for further investigations of the stereodivergent intermolecular cyclization mechanism, and highlight how nature has constructed this type of C2 symmetric molecule through intermolecular dimerization. ► Cloning and sequencing of a quartromicin biosynthetic gene cluster ► Reconstruction of the tetronate ring intermediates in vitro ► Production of two alternative polyketide chains by the same PKS assembly line ► A module skipping strategy in quartromicin biosynthesis Quartromicins possess a unique symmetrical structure with four spirotetronate units. He et al. show that the tetronate ring intermediates could be reconstructed in vitro and suggest a module skipping strategy for the production of two alternative polyketide chains by the same polyketide synthase assembly line.