The oxidative rearrangements in bacterial aromatic polyketide biosynthesis

Covering: up to April 2025Bacterial aromatic polyketides represent a notable class of natural products that have found extensive applications in clinical treatments. In their biosynthesis, oxidative rearrangements represent critical transformations that typically afford diverse scaffolds, structural rigidity, and biological activities. In this context, it is evident that redox enzymes are frequently implicated in various rearrangement processes, whereby they facilitate the transformation of pathway precursors into mature natural products. In this review, we will elucidate how natural enzymes utilize redox chemistry to create new carbon skeletons in the field of bacterial aromatic polyketide biosynthesis. Representative unique examples of Baeyer-Villiger and Favorskii-type oxidative rearrangements catalyzed by flavin-dependent monooxygenases, innovative carbon skeleton rearrangements catalyzed by ketoreductases and dioxygenases, as well as intermolecular dimerization catalyzed by CYP450s or NmrA-like proteins, are summarized and discussed. Concurrently, the structural characteristics and catalytic mechanisms of selected enzymes will also be introduced. By revealing the intriguing chemistry and enzymology behind these oxidative rearrangement transformations, this comprehensive review will not only enhance our comprehension of this uncommon chemical regularity but also provide potent biocatalysts for the semi-synthesis or synthetic biology of complex natural molecules.