Biochemical and Structural Insights of the N-Methyltransferase CyaF in Cyanogramide Biosynthesis.

IF 3.6 2区生物学 Q2 CHEMISTRY, MEDICINAL Journal of Natural Products Pub Date : 2025-03-28 Epub Date: 2025-03-07 DOI:10.1021/acs.jnatprod.4c01391

Ruijie Chen, Qingbo Zhang, Liping Zhang, Chunyan Fang, Hanning Zhu, Weiming Zhu, Changsheng Zhang, Yiguang Zhu

引用次数: 0

Abstract

N-Methyltransferases involved in indole methylation have seldom been discovered in natural product biosynthesis. This study focuses on the enzyme CyaF, which catalyzes a critical N-methylation step of indole in the β-carboline skeleton during cyanogramide biosynthesis. Seven β-carboline analogues (3-9) were isolated from the recombinant strain Streptomyces coelicolor YF11/cyaABC, including three new compounds (5-7). In vitro assays revealed CyaF's substrate flexibility. The crystal structure of the CyaF/S-adenosyl-L-homocysteine (SAH) complex, combined with the AlphaFold-predicted model and site-directed mutagenesis, elucidated the catalytic mechanism and structural features that enable CyaF to accommodate diverse substrates, highlighting its potential for biocatalytic applications.

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n -甲基转移酶CyaF在氰酰胺生物合成中的生化和结构研究。

参与吲哚甲基化的n -甲基转移酶在天然产物生物合成中很少被发现。本研究的重点是CyaF酶，该酶在氰酰胺生物合成过程中催化β-碳碱骨架中吲哚的关键n -甲基化步骤。从重组菌株colcololstreptomyces YF11/cyaABC中分离到7个β-碳碱类似物（3-9），包括3个新化合物（5-7）。体外实验揭示了CyaF的底物柔韧性。CyaF/ s -腺苷- l-同型半胱氨酸（SAH）复合物的晶体结构，结合alphafold预测模型和位点定向诱变，阐明了使CyaF适应多种底物的催化机制和结构特征，突出了其生物催化应用的潜力。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Natural Products 生物-药学

CiteScore

9.10

自引率

5.90%

发文量

294

审稿时长

2.3 months

期刊介绍： The Journal of Natural Products invites and publishes papers that make substantial and scholarly contributions to the area of natural products research. Contributions may relate to the chemistry and/or biochemistry of naturally occurring compounds or the biology of living systems from which they are obtained. Specifically, there may be articles that describe secondary metabolites of microorganisms, including antibiotics and mycotoxins; physiologically active compounds from terrestrial and marine plants and animals; biochemical studies, including biosynthesis and microbiological transformations; fermentation and plant tissue culture; the isolation, structure elucidation, and chemical synthesis of novel compounds from nature; and the pharmacology of compounds of natural origin. When new compounds are reported, manuscripts describing their biological activity are much preferred. Specifically, there may be articles that describe secondary metabolites of microorganisms, including antibiotics and mycotoxins; physiologically active compounds from terrestrial and marine plants and animals; biochemical studies, including biosynthesis and microbiological transformations; fermentation and plant tissue culture; the isolation, structure elucidation, and chemical synthesis of novel compounds from nature; and the pharmacology of compounds of natural origin.