嗜青霉产生的异氰酸抗生素代谢物匹诺曹素A的发现、生物活性和生物合成

IF 3.6 2区生物学 Q2 CHEMISTRY, MEDICINAL

Journal of Natural Products Pub Date : 2025-04-03 DOI:10.1021/acs.jnatprod.5c0017410.1021/acs.jnatprod.5c00174

Shinji Kishimoto*, Rikuto Takahashi, Akio Nagasawa and Kenji Watanabe*,

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引用次数: 0

摘要

我们从嗜青霉中发现了新的天然产物匹诺曹啉A(1)和B(2)，并通过降解和衍生化测定了这些化合物的立体化学性质。化合物1含有两个异氰化物基团，对革兰氏阳性菌具有抑菌活性，其抑菌活性取决于其铜螯合活性。通过异源表达多结构域异氰化物合成酶-非核糖体肽合成酶Pp_crmA和外排泵Pp_crmE，重建了化合物1的生物合成过程。这是真菌异源生产二异氰酸酯天然产物的第一篇报道，突出了CrmA家族酶的多步催化作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

Discovery, Biological Activity, and Biosynthesis of Pinocicolin A, an Antibiotic Isocyanide Metabolite Produced by Penicillium pinophilum

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Discovery, Biological Activity, and Biosynthesis of Pinocicolin A, an Antibiotic Isocyanide Metabolite Produced by Penicillium pinophilum

We discovered new natural products pinocicolins A (1) and B (2) from Penicillium pinophilum and determined the stereochemistry of these compounds by degradation and derivatization. Compound 1, containing two isocyanide groups, exhibited bacteriostatic activity against Gram-positive bacteria depending upon its copper-chelating activity. The biosynthesis of compound 1 was reconstructed in Aspergillus nidulans by heterologous expression of multidomain isocyanide synthase–nonribosomal peptide synthetase Pp_crmA and efflux pump Pp_crmE. This is the first report of the heterologous production of a fungal diisocyanide natural product, highlighting the multistep catalysis of CrmA family enzymes.

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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.