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Revised Structure of Anthelvencin A and Characterization of the Anthelvencin Biosynthetic Gene Cluster.
ACS Chemical Biology ( IF 3.5 ) Pub Date : 2020-03-04 , DOI: 10.1021/acschembio.9b00960
Céline Aubry 1 , Paolo Clerici 2 , Claude Gerbaud 1 , Laurent Micouin 2 , Jean-Luc Pernodet 1 , Sylvie Lautru 1
Affiliation  

Anthelvencins A and B are pyrrolamide metabolites produced by Streptomyces venezuelae ATCC 14583 and 14585. Isolated in 1965, they were reported to exhibit anthelmintic and moderate antibacterial activities. In this study, we revise the structure of anthelvencin A and identify a third anthelvencin metabolite, bearing two N-methylated pyrrole groups, which we named anthelvencin C. We sequenced the genome of S. venezuelae ATCC 14583 and identified a gene cluster predicted to direct the biosynthesis of anthelvencins. Functional analysis of this gene cluster confirmed its involvement in anthelvencin biosynthesis and allowed us to propose a biosynthetic pathway for anthelvencins. In addition to a nonribosomal peptide synthetase (NRPS), the assembly of anthelvencins involves an enzyme from the ATP-grasp ligase family, Ant23. We propose that Ant23 uses a PCP-loaded 4-aminopyrrole-2-carboxylate as substrate. As observed for the biosynthesis of the other pyrrolamides congocidine (produced by Streptomyces ambofaciens ATCC 25877) and distamycin (produced by Streptomyces netropsis DSM 40846), the NRPS assembling anthelvencins is composed of stand-alone domains only. Such NRPSs, sometimes called type II NRPSs, are less studied than the classical multimodular NRPSs. Yet, they constitute an interesting model to study protein-protein interactions in NRPSs and are good candidates for combinatorial biosynthesis approaches.

中文翻译:

修改过的安德文霉素A的结构和安德文霉素生物合成基因簇的表征。

安特万星A和B是委内瑞斯链霉菌ATCC 14583和14585产生的吡咯酰胺代谢产物。1965年分离,据报道它们具有驱虫和中度抗菌活性。在这项研究中,我们修改了蒽铁霉素A的结构,并鉴定了带有两个N-甲基化吡咯基团的第三蒽铁代谢物,我们将其命名为蒽铁霉素C。我们对委内瑞拉链球菌ATCC 14583的基因组进行了测序,并鉴定了预计可指导直接遗传的基因簇花粉生物素的生物合成。该基因簇的功能分析证实了它参与了蒽醌的生物合成,并允许我们提出蒽醌的生物合成途径。除非核糖体肽合成酶(NRPS)外,蒽醌素的组装还涉及来自ATP抓握连接酶家族的一种酶Ant23。我们建议Ant23使用负载PCP的4-氨基吡咯-2-羧酸盐作为底物。如观察到其他吡咯酰胺酰胺刚果(由Streptomyces ambofaciens ATCC 25877生产)和双歧霉素(由Streptomyces netropsis DSM 40846生产)的生物合成所示,NRPS组装蒽醌仅由独立域组成。与经典的多模块NRPS相比,此类NRPS(有时称为II型NRPS)的研究较少。然而,它们构成了研究NRPS中蛋白质相互作用的有趣模型,并且是组合生物合成方法的良好候选者。NRPS组装花粉蛋白仅由独立结构域组成。与经典的多模块NRPS相比,此类NRPS(有时称为II型NRPS)的研究较少。然而,它们构成了研究NRPS中蛋白质相互作用的有趣模型,并且是组合生物合成方法的良好候选者。NRPS组装花粉蛋白仅由独立结构域组成。与经典的多模块NRPS相比,此类NRPS(有时称为II型NRPS)的研究较少。然而,它们构成了研究NRPS中蛋白质相互作用的有趣模型,并且是组合生物合成方法的良好候选者。
更新日期:2020-04-23
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