黄素依赖性单加氧酶 Kmy13 在肯多霉素 B 的生物合成过程中介导羰环安萨系统的形成

IF 15.6 1区化学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Journal of the American Chemical Society Pub Date : 2024-10-06 DOI:10.1021/jacs.4c0877410.1021/jacs.4c08774

Jiang Chen, Hongjie Zhu, Ming Peng, Shanwen Zhang, Qinglian Li, Yu-Cheng Gu and Jianhua Ju*,

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引用次数: 0

摘要

Kendomycin B 与其他ansamycins 的区别在于其独特的全碳源ansa支架。我们在此表明，依赖于 FAD 的单加氧酶 Kmy13 是安装罕见的 ansa 结构框架的唯一责任者；我们详细介绍了体内基因破坏/补充实验和体外酶学测定。此外，带有 β-酮酯的化合物 kendolactone A (2) 被证实是 Kmy13 的天然底物，也是通向 kendomycin B 的真正生物合成中间体。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

Flavin-Dependent Monooxygenase Kmy13 Mediates Formation of the Carbocyclic ansa System during Kendomycin B Biosynthesis

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Flavin-Dependent Monooxygenase Kmy13 Mediates Formation of the Carbocyclic ansa System during Kendomycin B Biosynthesis

Kendomycin B is distinguished from other ansamycins by its unique, fully carbogenic ansa scaffold. We show here that FAD-dependent monooxygenase Kmy13 is solely responsible for installing the rare ansa structural framework; in vivo gene disruption/complementation experiments and in vitro enzymatic assays are described in detail. Moreover, the compound with a β-keto ester, kendolactone A (2), was confirmed as the natural substrate of Kmy13 and a bona fide biosynthetic intermediate en route to kendomycin B. Further structural prediction and biochemical assays have provided significant insights into the catalytic mechanism of Kmy13.

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来源期刊

Journal of the American Chemical Society 化学-化学综合

CiteScore

24.40

自引率

6.00%

发文量

2398

审稿时长

1.6 months

期刊介绍： The flagship journal of the American Chemical Society, known as the Journal of the American Chemical Society (JACS), has been a prestigious publication since its establishment in 1879. It holds a preeminent position in the field of chemistry and related interdisciplinary sciences. JACS is committed to disseminating cutting-edge research papers, covering a wide range of topics, and encompasses approximately 19,000 pages of Articles, Communications, and Perspectives annually. With a weekly publication frequency, JACS plays a vital role in advancing the field of chemistry by providing essential research.