Genome-Led Discovery of the Antibacterial Cyclic Lipopeptide Kutzneridine A and Its Silent Biosynthetic Gene Cluster from Kutzneria Species.

IF 3.3 2区生物学 Q2 CHEMISTRY, MEDICINAL Journal of Natural Products Pub Date : 2024-10-25 Epub Date: 2024-09-27 DOI:10.1021/acs.jnatprod.4c00633

Francisco Javier Ortiz-López, Daniel Oves-Costales, Jaime Felipe Guerrero Garzón, Tetiana Gren, Eva Baggesgaard Sterndorff, Xinglin Jiang, Tue Sparholt Jo Rgensen, Kai Blin, Ignacio Fernández-Pastor, José R Tormo, Jesús Martín, Pilar Sánchez, Mercedes de la Cruz Moreno, Fernando Reyes, Olga Genilloud, Tilmann Weber

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Abstract

Genome analysis of Kutzneria sp. CA-103260 revealed a putative lipopeptide-encoding biosynthetic gene cluster (BGC) that was cloned into a bacterial artificial chromosome (BAC) and heterologously expressed in Streptomyces coelicolor M1152. As a result, a novel cyclic lipo-tetrapeptide containing two diaminopropionic acid residues and an exotic N,N-acetonide ring, kutzneridine A (1), was isolated and structurally characterized. Evaluation of the extraction conditions and isotope-labeling chemical modifications showed that the acetonide ring originated from acetone during isolation. The BGC was analyzed in silico and a biosynthetic pathway to 1 was proposed. Kutzneridine A displayed remarkable antibacterial activity against methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococci.

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通过基因组发现库茨内里藻抗菌环脂肽 Kutzneridine A 及其沉默生物合成基因簇。

Kutzneria sp. CA-103260的基因组分析发现了一个假定的脂肽编码生物合成基因簇（BGC），该基因簇被克隆到细菌人工染色体（BAC）中，并在链霉菌（Streptomyces coelicolor）M1152中进行异源表达。结果分离出了一种新型环脂四肽--kutzneridine A (1)，它含有两个二氨基丙酸残基和一个奇特的 N,N-丙酮环，并具有结构特征。对提取条件和同位素标记化学修饰的评估表明，丙酮环在分离过程中来自丙酮。对 BGC 进行了硅学分析，并提出了 1 的生物合成途径。Kutzneridine A 对耐甲氧西林金黄色葡萄球菌和耐万古霉素肠球菌具有显著的抗菌活性。

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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.