Recent Advances in Discovery, Structure, Bioactivity, and Biosynthesis of trans-AT Polyketides.

Abstract

Bacterial trans-acyltransferase polyketide synthases (trans-AT PKSs) are among the most complex enzymes, which are responsible for generating a wide range of natural products, identified as trans-AT polyketides. These polyketides have received significant attention in drug development due to their structural diversity and potent bioactivities. With approximately 300 synthesized molecules discovered so far, trans-AT PKSs are found widespread in bacteria. Their biosynthesis pathways exhibit considerable genetic diversity, leading to the emergence of numerous enzymes with novel mechanisms, serving as a valuable resource for genetic engineering aimed at modifying small molecules' structures and creating new engineered enzymes. Despite the systematic discussions on trans-AT polyketides and their biosynthesis in earlier studies, the continuous advancements in tools, methods, compound identification, and biosynthetic pathways require a fresh update on accumulated knowledge. This review seeks to provide a comprehensive discussion for the 27 types of trans-AT polyketides discovered within the last seven years, detailing their sources, structures, biological activities, and biosynthetic pathways. By reviewing this new knowledge, a more profound understanding of the trans-AT polyketide family can be achieved.