title: A two-step sulfation in antibiotic biosynthesis requires a type III polyketide synthase.
abstract: 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″-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'-phosphoadenosine-5'-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 III PKS to generate a chemical reagent in bacterial sulfate metabolism.
authors.affiliation: Pharmaceutical Institute, University of Tübingen, Tübingen, Germany.
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Tang
authors.forename: Kornelia
authors.initials: K
authors.lastname: Eitel
authors.forename: Leonard
authors.initials: L
authors.lastname: Kaysser
authors.forename: Andreas
authors.initials: A
authors.lastname: Kulik
authors.forename: Stephanie
authors.initials: S
authors.lastname: Grond
authors.forename: Bertolt
authors.initials: B
authors.lastname: Gust
mesh_terms: D000217:Acyltransferases / Q000145:classification / Q000378:metabolism*; D000900:Anti-Bacterial Agents / Q000096:biosynthesis* / Q000737:chemistry; D015394:Molecular Structure; D013431:Sulfates / Q000737:chemistry / Q000378:metabolism*
chemical_list: D000900:Anti-Bacterial Agents; D013431:Sulfates; D000217:Acyltransferases; C020141:flavanone synthetase
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