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厌氧菌中多种抗菌和抗增殖丙酰醇的生物合成。

Biosynthesis of Diverse Antimicrobial and Antiproliferative Acyloins in Anaerobic Bacteria.

机构信息

Department of Biomolecular Chemistry , Leibniz Institute for Natural Product Research and Infection Biology (HKI) , Beutenbergstr. 11a , 07745 Jena , Germany.

BioPilot Plant , Leibniz Institute for Natural Product Research and Infection Biology (HKI) , Beutenbergstr. 11a , 07745 Jena , Germany.

出版信息

ACS Chem Biol. 2019 Jul 19;14(7):1490-1497. doi: 10.1021/acschembio.9b00228. Epub 2019 Jun 21.

DOI:10.1021/acschembio.9b00228
PMID:31243958
Abstract

Metabolic profiling and genome mining revealed that anaerobic bacteria have the potential to produce acyloin natural products. In addition to sattazolin A and B, three new sattazolin congeners and a novel acyloin named clostrocyloin were isolated from three strains of , a bacterium used for industrial solvent production. Bioactivity profiling showed that the sattazolin derivatives possess antimicrobial activities against mycobacteria and pseudomonads with only low cytotoxicity. Clostrocyloin was found to be mainly active against fungi. The thiamine diphosphate (ThDP)-dependent sattazolin-producing synthase was identified and characterized both and in enzyme assays. A related acyloin synthase from the clostrocyloin producer was shown to be responsible for the production of the acyloin core of clostrocyloin. The biotransformation experiments provided first insights into the substrate scope of the clostrocyloin synthase and revealed biosynthetic intermediates.

摘要

代谢组学和基因组挖掘表明,厌氧菌有可能产生酰基醇天然产物。从用于工业溶剂生产的细菌中分离到三种新的 sattazolin 同系物和一种新型酰基醇命名为 clostrocyloin。除了 sattazolin A 和 B 之外,生物活性分析表明,sattazolin 衍生物对分枝杆菌和假单胞菌具有抗菌活性,且细胞毒性低。Clostrocyloin 主要对真菌有活性。发现依赖硫胺素二磷酸 (ThDP) 的 sattazolin 产生合酶在 和 酶测定中均被鉴定和表征。来自 clostrocyloin 产生菌的相关酰基醇合酶被证明负责产生 clostrocyloin 的酰基醇核心。生物转化实验首次深入了解了 clostrocyloin 合酶的底物范围,并揭示了生物合成中间体。

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