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应激驱动的发现:热液喷口来源的链霉菌 WU20 产生的新型隐丹参酮类抗生素,采用整合代谢组学策略。

Stress-driven discovery of a cryptic antibiotic produced by Streptomyces sp. WU20 from Kueishantao hydrothermal vent with an integrated metabolomics strategy.

机构信息

Ocean College, Zhejiang University, Hangzhou, 310058, Republic of China.

Institute of Marine Geology and Chemistry, National Sun Yat-sen University, Kaohsiung, 80424, Taiwan, Republic of China.

出版信息

Appl Microbiol Biotechnol. 2017 Feb;101(4):1395-1408. doi: 10.1007/s00253-016-7823-y. Epub 2016 Oct 11.

DOI:10.1007/s00253-016-7823-y
PMID:27730337
Abstract

Marine hydrothermal microorganisms respond rapidly to the changes in the concentrations and availability of metals within hydrothermal vent microbial habitats which are strongly influenced by elevated levels of heavy metals. Most hydrothermal vent actinomycetes possess a remarkable capability for the synthesis of a broad variety of biologically active secondary metabolites. Major challenges in the screening of these microorganisms are to activate the expression of cryptic biosynthetic gene clusters and the development of technologies for efficient dereplication of known compounds. Here, we report the identification of a novel antibiotic produced by Streptomyces sp. WU20 isolated from the metal-rich hydrothermal vents in Taiwan Kueishantao, following a strategy based on metal induction of silent genes combined with metabolomics analytical methods. HPLC-guided isolation by tracking the target peak resulted in the characterization of the novel compound 1 with antimicrobial activity against Bacillus subtilis. The stress metabolite 1 induced by nickel is structurally totally different compared with the normally produced compounds. This study underlines the applicability of metal induction combined with metabolic analytical techniques in accelerating the exploration of novel antibiotics and other medically relevant natural products.

摘要

海洋热液微生物对热液喷口微生物栖息地中金属浓度和可用性的变化反应迅速,而金属浓度和可用性的变化受到重金属水平升高的强烈影响。大多数热液喷口放线菌具有合成多种生物活性次级代谢物的显著能力。筛选这些微生物的主要挑战在于激活隐匿生物合成基因簇的表达,以及开发有效的已知化合物去重复技术。在这里,我们报道了一种新型抗生素的鉴定,该抗生素由台湾龟山热液喷口富含金属的土壤中分离的链霉菌属 sp. WU20 产生,该抗生素的鉴定是基于沉默基因的金属诱导与代谢组学分析方法相结合的策略。通过跟踪目标峰进行 HPLC 引导分离,导致了具有抗枯草芽孢杆菌活性的新型化合物 1 的表征。镍诱导的应激代谢物 1 与正常产生的化合物在结构上完全不同。这项研究强调了金属诱导与代谢分析技术相结合在加速新型抗生素和其他医学相关天然产物的探索中的适用性。

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