Biosynthesis of chuangxinmycin featuring a deubiquitinase-like sulfurtransferase.
Biosynthesis of chuangxinmycin featuring a deubiquitinase-like sulfurtransferase.
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DOI：
10.1002/anie.202107745
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发表时间：
2021-09
影响因子：
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通讯作者：
Xingwang Zhang;Xiaokun Xu;C. You;Chao‐Yu Yang;Jiawei Guo;Moli Sang;Ce Geng;Fangyuan Cheng;L. Du;Yuemao Shen;Sheng Wang;Haidong Lan;Fan Yang;Yue-zhong Li;Ya-Jie Tang;Youming Zhang;Xiaoying Bian;Shengying Li;Wei Zhang
中科院分区：
文献类型：
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作者：
Xingwang Zhang;Xiaokun Xu;C. You;Chao‐Yu Yang;Jiawei Guo;Moli Sang;Ce Geng;Fangyuan Cheng;L. Du;Yuemao Shen;Sheng Wang;Haidong Lan;Fan Yang;Yue-zhong Li;Ya-Jie Tang;Youming Zhang;Xiaoying Bian;Shengying Li;Wei Zhang
硫是所有生命所必需的元素，因为它能形成各种含硫分子。与已有的生物学功能相比，人们对含硫分子生物合成中的硫掺入机理的了解还很有限。创辛霉素是一种含硫抗生素，具有独特的硫代并[4，3，2-CD]吲哚(TPI)骨架，对细菌色氨酸-tRNA合成酶具有选择性抑制活性。尽管已经报道了生物合成的基因簇，以及最近对负责C-S键形成的P450酶的功能进行了表征，但硫结合的酶机制仍然不清楚。在这里，我们通过关键酶的体外生化特征来解决这个中心生物合成问题，并在一锅酶反应中重建TPI骨架。特别是，我们揭示了JAMM/MPN+蛋白CxM3通过与泛素样硫载体蛋白Cxm4GG相互作用，作为去泛素酶样硫转移酶来催化非经典的硫转移反应。这一发现为自然界中的硫转移酶增加了一种新的机制。
Sulfur is an essential element for all life by forming various sulfur-containing molecules. Compared to the well-studied biological functions, the knowledge on sulfur incorporation mechanism involved in sulfur-containing molecule biosynthesis remains limited. Chuangxinmycin is a sulfur-containing antibiotic with a unique thiopyrano[4,3,2- cd ]indole (TPI) skeleton and selective inhibitory activity against bacterial tryptophanyl-tRNA synthetase. Despite the previously reported biosynthetic gene clusters and the recent functional characterization of a P450 enzyme responsible for C-S bond formation, the enzymatic mechanism for sulfur incorporation remains unknown. Here, we resolve this central biosynthetic problem by in vitro biochemical characterization of the key enzymes, and reconstitute the TPI skeleton in a one-pot enzymatic reaction. Particularly, we reveal that the JAMM/MPN + protein Cxm3 functions as a deubiquitinase-like sulfurtransferase to catalyze a non-classical sulfur-transfer reaction by interacting with the ubiquitin-like sulfur carrier protein Cxm4GG. This finding adds a new mechanism for sulfurtransferase in nature.