New Insights into the Biosynthesis of Fosfazinomycin.
New Insights into the Biosynthesis of Fosfazinomycin.
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DOI：
10.1039/c6sc01389a
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发表时间：
2016
期刊：
影响因子：
8.4
通讯作者：
van der Donk WA
中科院分区：
文献类型：
--
作者：
Huang Z;Wang KA;van der Donk WA
研究了膦酸盐天然产物fosfazinomycin中独特的肼段的生物合成起源。膦酸盐天然产物fosfazinomycin中独特的肼段的生物合成起源尚不清楚。本研究介绍了其基因簇中编码的五个蛋白的活性。黄素依赖性加氧酶FzmM催化l-Asp氧化为n-羟基asp。当加入FzmL时，除生成亚硝酸外，还生成富马酸盐。腺苷琥珀酸裂解酶同源物FzmR能从n -乙酰基琥珀酸肼中去除乙酰肼，而n -乙酰基琥珀酸肼是fzmq催化的琥珀酸肼乙酰化的产物。总的来说，这些发现提示了从l-Asp到n -乙酰肼的途径。同位素标记研究证实了磷霉素中含有l-Asp中的氮。fosfazinomycin n端Val的安装是由FzmI催化的，这是一个依赖于Val- trna的过程。
The biosynthetic origin of a unique hydrazide moiety in the phosphonate natural product fosfazinomycin is investigated. The biosynthetic origin of a unique hydrazide moiety in the phosphonate natural product fosfazinomycin is unknown. This study presents the activities of five proteins encoded in its gene cluster. The flavin-dependent oxygenase FzmM catalyses the oxidation of l-Asp to N-hydroxy-Asp. When FzmL is added, fumarate is produced in addition to nitrous acid. The adenylosuccinate lyase homolog FzmR eliminates acetylhydrazine from N-acetyl-hydrazinosuccinate, which in turn is the product of FzmQ-catalysed acetylation of hydrazinosuccinate. Collectively, these findings suggest a path to N-acetylhydrazine from l-Asp. The incorporation of nitrogen from l-Asp into fosfazinomycin was confirmed by isotope labelling studies. Installation of the N-terminal Val of fosfazinomycin is catalysed by FzmI in a Val-tRNA dependent process.