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发现源于 sp. SH-C52 的线性脯氨酸八肽化合物 Thanafactin A,受基因组挖掘启发。

Discovery of Thanafactin A, a Linear, Proline-Containing Octalipopeptide from sp. SH-C52, Motivated by Genome Mining.

机构信息

Pharmaceutical Institute, Department of Pharmaceutical Biology, University of Tübingen, 72076 Tübingen, Germany.

Pharmaceutical Institute, Pharmaceutical & Medicinal Chemistry, University of Bonn, 53121 Bonn, Germany.

出版信息

J Nat Prod. 2021 Jan 22;84(1):101-109. doi: 10.1021/acs.jnatprod.0c01174. Epub 2020 Dec 31.

DOI:10.1021/acs.jnatprod.0c01174
PMID:33382250
Abstract

Genome mining of the bacterial strains sp. SH-C52 and DSM 11579 showed that both strains contained a highly similar gene cluster encoding an octamodular nonribosomal peptide synthetase (NRPS) system which was not associated with a known secondary metabolite. Insertional mutagenesis of an NRPS component followed by comparative profiling led to the discovery of the corresponding novel linear octalipopeptide thanafactin A, which was subsequently isolated and its structure determined by two-dimensional NMR and further spectroscopic and chromatographic methods. In bioassays, thanafactin A exhibited weak protease inhibitory activity and was found to modulate swarming motility in a strain-specific manner.

摘要

从细菌菌株 sp. SH-C52 和 DSM 11579 中进行基因组挖掘表明,这两个菌株都含有一个高度相似的基因簇,编码一个八模块非核糖体肽合成酶(NRPS)系统,该系统与已知的次级代谢产物无关。对 NRPS 成分进行插入诱变,然后进行比较分析,导致发现了相应的新型线性八肽脂肽 thanafactin A,随后对其进行了分离,并通过二维 NMR 以及进一步的光谱和色谱方法确定了其结构。在生物测定中,thanafactin A 表现出较弱的蛋白酶抑制活性,并发现其以菌株特异性方式调节 swarm 运动。

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