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

IF 3.3 2区生物学 Q2 CHEMISTRY, MEDICINAL

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

Shinji Kishimoto, Rikuto Takahashi, Akio Nagasawa, Kenji Watanabe

引用次数: 0

Abstract

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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我们从嗜酸青霉菌中发现了新的天然产物蒎烷醇素 A（1）和 B（2），并通过降解和衍生化确定了这些化合物的立体化学结构。化合物 1 含有两个异氰基团，对革兰氏阳性细菌具有抑菌活性，这取决于它的铜螯合活性。通过异源表达多域异氰酸合成酶-非核糖体肽合成酶 Pp_crmA 和外排泵 Pp_crmE，在黑曲霉中重建了化合物 1 的生物合成过程。这是首次报道异源生产真菌二异氰酸酯天然产物，凸显了 CrmA 家族酶的多步催化过程。

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.