A two-step sulfation in antibiotic biosynthesis requires a type III polyketide synthase

作者：Tang Xiaoyu^*; Eitel Kornelia; Kaysser Leonard; Kulik Andreas; Grond Stephanie; Gust Bertolt

来源：Nature Chemical Biology, 2013, 9(10): 610-615.

DOI：10.1038/NCHEMBIO.1310

Caprazamycins (CPZs) belong to a group of liponucleoside antibiotics inhibiting the bacterial MraY translocase, an essential enzyme involved in peptidoglycan biosynthesis. We have recently identified analogs that are decorated with a sulfate group at the 2 %26apos;%26apos;-hydroxy of the aminoribosyl moiety, and we now report an unprecedented two-step sulfation mechanism during the biosynthesis of CPZs. A type III polyketide synthase (PKS) known as Cpz6 is used in the biosynthesis of a group of new triketide pyrones that are subsequently sulfated by an unusual 3%26apos;-phosphoadenosine-5%26apos;-phosphosulfate (PAPS)-dependent sulfotransferase (Cpz8) to yield phenolic sulfate esters, which serve as sulfate donors for a PAPS-independent arylsulfate sulfotransferase (Cpz4) to generate sulfated CPZs. This finding is to our knowledge the first demonstration of genuine sulfate donors for an arylsulfate sulfotransferase and the first report of a type Ill PKS to generate a chemical reagent in bacterial sulfate metabolism.

• 出版日期2013-10