Elucidation of Acetyl-Branched Sugar Pathway in Type II Polyketide Biosynthesis via One-Pot Enzymatic Synthesis

Acetyl-branched sugars, although relatively rare, are found in certain natural products with notable bioactivities. Herein, we biochemically investigated the biosynthetic pathway of this rare sugar in type II polyketides featuring one-pot enzymatic synthesis of the key acetyl-branched TDP-sugar. The evidence shows that TjhB9/B10 were responsible for the attachment of an acetyl unit, a glycosyltransferase TjhB3 guided the uploading of a branched sugar, and a C7 reductase encoded by a gene outside the biosynthetic gene cluster subsequently reduced the TjhB3 product. Collectively, these results elucidated the sugar tailoring pathway of acetyl-branched sugar-modified polyketides.