Despite the wealth of physiological knowledge and plentiful genomes available, only few natural products of anaerobic bacteria have been identified until today and even less have been linked to their biosynthetic gene cluster. Here, we analyzed a unique NRPS-PKS hybrid gene cluster from an anaerobic Epsilonproteobacterium (Sulfurospirillum barnesii). Phylogenetic analysis of key biosynthetic genes, gene expression studies, and comparative metabolomics resulted in the identification of the first anoxically biosynthesized NRPS-PKS hybrid metabolite: a lipo-dipeptide with a vinylogous side chain, called barnesin A. The absolute structure was verified by a modular total synthesis, and barnesin and derivatives were found to have antimicrobial activity, as well as selective and nanomolar inhibitory activity, against pharmacological important cysteine proteases, such as cathepsin B.

中文翻译：

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Barnesin A的生物合成，合成和活性，Barnesin A是一种由厌氧性psi肠杆菌产生的NRPS-PKS杂种。

尽管拥有丰富的生理知识和丰富的基因组，但直到今天，人们仍很少确认到厌氧细菌的天然产物，而且与其厌氧菌的生物合成基因簇相关的甚至更少。在这里，我们分析了厌氧性厄氏杆菌（Sulfurospirillum barnesii）的一个独特的NRPS-PKS杂种基因簇。）。通过对关键生物合成基因的系统发生分析，基因表达研究和比较代谢组学，鉴定出了第一个通过厌氧生物合成的NRPS-PKS杂化代谢产物：一种具有乙烯基侧链的脂二肽，称为barnesinA。模块化总合成，发现barnesin和衍生物对药理学重要的半胱氨酸蛋白酶（例如组织蛋白酶B）具有抗菌活性以及选择性和纳摩尔抑制活性。