A two-step sulfation in antibiotic biosynthesis requires a type III polyketide synthase.
A two-step sulfation in antibiotic biosynthesis requires a type III polyketide synthase.
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DOI：
10.1038/nchembio.1310
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发表时间：
2013-10
影响因子：
14.8
通讯作者：
Xiaoyu Tang;Kornelia Eitel;Leonard Kaysser;A. Kulik;S. Grond;B. Gust
中科院分区：
文献类型：
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作者：
Xiaoyu Tang;Kornelia Eitel;Leonard Kaysser;A. Kulik;S. Grond;B. Gust
Caprazamycins（CPZ）属于一组抑制细菌MraY移位酶的脂核苷抗生素，所述MraY移位酶是参与肽聚糖生物合成的必需酶。我们最近发现了在氨基核糖基部分的2″-羟基上修饰有硫酸酯基团的类似物，我们现在报告了CPZ生物合成过程中前所未有的两步硫酸化机制。一种III型聚酮化合物合成酶（PKS）Cpz 6被用于一组新的三酮化合物吡喃酮的生物合成中，这些吡喃酮随后被不寻常的3′-磷酸腺苷-5 ′-磷酸硫酸（PAPS）依赖性磺基转移酶（Cpz 8）硫酸化以产生酚硫酸酯，酚硫酸酯作为不依赖于PAPS的芳基硫酸酯磺基转移酶（Cpz 4）的硫酸酯供体以产生硫酸化的CPZ。据我们所知，这一发现是芳基硫酸盐磺基转移酶的真正硫酸盐供体的第一次证明，也是第一次报告III型PKS在细菌硫酸盐代谢中产生化学试剂。
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.