Pharmaceutical Institute, University of Tübingen, Tübingen, Germany.
Nat Chem Biol. 2013 Oct;9(10):610-5. doi: 10.1038/nchembio.1310. Epub 2013 Aug 4.
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.
卡普拉霉素（CPZs）属于一类抑制细菌 MraY 转位酶的脂核苷抗生素，该酶是参与肽聚糖生物合成的必需酶。我们最近鉴定出的类似物在氨基核糖部分的 2″-羟基上带有硫酸基，我们现在报告 CPZs 生物合成过程中一个前所未有的两步硫酸化机制。一种称为 Cpz6 的 III 型聚酮合酶（PKS）用于合成一组新的三酮吡喃，随后由一种不寻常的 3′-磷酸腺苷-5′-磷酸硫酸（PAPS）依赖性硫酸转移酶（Cpz8）硫酸化生成酚硫酸酯，这些酯作为硫酸盐供体用于 PAPS 非依赖性芳基硫酸盐硫酸转移酶（Cpz4）生成硫酸化 CPZs。据我们所知，这一发现首次证明了芳基硫酸盐硫酸转移酶的真正硫酸盐供体，也是 III 型 PKS 首次在细菌硫酸盐代谢中生成化学试剂的报道。
