Genome Mining of Linaridins Provides Insights into the Widely Distributed LinC Oxidoreductases

IF 3.3 2区生物学 Q2 CHEMISTRY, MEDICINAL

Journal of Natural Products Pub Date : 2023-10-11 DOI:10.1021/acs.jnatprod.3c00527

Meng-Xue Guo, Meng-Meng Zhang, Ke Sun, Jiao-Jiao Cui, Yi-Cheng Liu, Kun Gao, Shi-Hui Dong and Shangwen Luo*,

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Abstract

Linaridins are a family of underexplored ribosomally synthesized and post-translationally modified peptides despite the prevalence of their biosynthetic gene clusters (BGCs) in microbial genomes, as shown by bioinformatic studies. Our genome mining efforts reveal that 96 putative oxidoreductase genes, namely, LinC, are encoded in linaridin BGCs. We heterologously expressed two such LinC-containing linaridin BGCs, yan and ydn, from Streptomyces yunnanensis and obtained three new linaridins, named yunnanaridins A–C (1–3). Their structures are characterized by Z-configurations of the dehydrobutyrines and the presence of a variety of epimerized amino acid residues. Yunnanaridin A (1) is the sixth member of the family of type-B linaridins, whereas yunnanaridins B (2) and C (3) represent the first examples of expressed type-C linaridins. Interestingly, heterologous expression of the same BGCs with LinC in-frame knockouts produced the same compounds. This work expands the structural diversity of linaridins and provides evidence for the notion that the widespread LinCs may not be involved in linaridin biosynthesis.

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Linaridins的基因组挖掘为广泛分布的LinC氧化还原酶提供了见解。

如生物信息学研究所示，尽管Linaridins的生物合成基因簇（BGCs）在微生物基因组中普遍存在，但它是一个未被充分探索的核糖体合成和翻译后修饰肽家族。我们的基因组挖掘工作揭示了96个假定的氧化还原酶基因，即LinC，编码在林丙啶BGCs中。我们从云南链霉菌中异源表达了两个这样的含有LinC的linaridin BGCs，yan和ydn，并获得了三个新的linariding，命名为yunnanaridins A-C（1-3）。它们的结构以脱氢丁酰胺的Z构型和各种差向异构氨基酸残基的存在为特征。Yunnanaridin A（1）是B型哌啶家族的第六个成员，而yunnanaritin B（2）和C（3）代表表达的C型哌啶的第一个实例。有趣的是，在框敲除中用LinC异源表达相同的BGC产生相同的化合物。这项工作扩展了林丙啶的结构多样性，并为广泛存在的林丙啶可能不参与林丙啶生物合成的概念提供了证据。

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.