Investigation of the Molecular Landscape of Bacterial Aromatic Polyketides by Global Analysis of Type II Polyketide Synthases

Aromatic polyketides biosynthesized by microorganisms are a prominent class of natural products widely used in clinical treatments. Although genome mining approaches have accelerated the discovery of these molecules, the molecular diversity, abundance, and distribution of bacterial aromatic polyketides at a global scale remain elusive. Here, we provide a global atlas of bacterial aromatic polyketides based on large-scale analysis of type II polyketide synthases. We first established the chain length factor protein as a marker that can predict both chemical class and molecular uniqueness of the biosynthetic product, and analyzed the abundance, taxonomic distribution, estimated structural diversity, and the total number of aromatic polyketides in bacteria. We further show the identification of oryzanaphthopyrans with an unprecedented angular naphthopyran scaffold from a rare actinobacterium by genome mining guided by the global atlas. These results serve as a compass for exploiting the entire type II polyketide synthase-derived aromatic polyketides in bacteria.