Advances on structure, bioactivity, and biosynthesis of amino acid-containing trans-AT polyketides

Trans-AT polyketides represent a class of natural compounds utilizing independent acyltransferase during their biosynthesis. They are well known for their diverse chemical structures and potent bioactivities. Trans-AT polyketides are synthesized through biosynthetic gene clusters predominantly composed of polyketide synthases (PKS), but often found in hybrid with non-ribosomal peptide synthetases (NRPS). This genetic hybridization results in the incorporation of amino acid residues into polyketide structures, significantly enhancing their structural diversity. Numerous amino acid-containing trans-AT polyketides have been identified, drawing significant attention to the mechanisms underlying amino acid incorporation and their impact on the biological activity of polyketides. Here, we discussed their origins, structures, biological activities, and the specific roles of amino acids in modulating both the bioactivity and biosynthesis of 38 trans-AT polyketides containing amino acids for the first time. This comprehensive analysis will serve as a crucial reference for the exploration of novel compounds and the improvement of structures and activities.