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Exploring new avenues of growth and secondary metabolite production by antibiotic-producing Streptomyces bacteria

探索产抗生素链霉菌生长和次生代谢产物生产的新途径

基本信息

批准号：
418836285
负责人：
Dr. Tina Netzker
金额：
--
依托单位：
Leibniz-Institut für Alternsforschung - Fritz-Lipmann-Institut e.V. (FLI)
依托单位国家：
德国
项目类别：
Research Fellowships
财政年份：
2019
资助国家：
德国
起止时间：
2018-12-31 至 2021-12-31
项目状态：
已结题

来源：
https://gepris.dfg.de/gepris/projekt/418836285?language=en
关键词：
Exploring new avenues growth secondary

项目摘要

Streptomyces bacteria are of major scientific interest due to their extraordinary life cycle and their prolific secondary metabolism, the products of which include the majority of clinically prescribed antibiotics. The metabolic potential of the streptomycetes has not been fully exploited, and they are looked upon as being important sources of new antibiotics that can help in treating antibiotic resistant infections. A more holistic understanding of Streptomyces biology will allow for effective exploitation of their unique metabolic and developmental capabilities. Recent work has revealed the model organism Streptomyces venezuelae can abscond from its classical life cycle when confronted with fungi or a nutrient-poor environment, using a newly described growth behaviour called exploratory growth. Explorer cells grow as non-branching vegetative hyphae and have a much faster growth rate compared with the "normal" vegetative hyphae. Interestingly, exploration does not dependent on classical developmental regulators, suggesting it represents a new form of growth. Streptomyces exploration provides an outstanding system with which to elucidate the molecular and regulatory mechanisms of microbial communication, microbial development and secondary metabolism. Based on RNA-sequencing analyses and chemical mutagenesis, several genes have been confirmed to be involved in the regulation of exploratory growth. Additionally, altered expression of secondary metabolite clusters has been detected. Using complementary genetic, biochemical, cell biological and metabolic analyses, the proposed project will investigate how exploration is regulated, with special focus on the unique mechanism of colony expansion, and how exploration affects secondary metabolite production. This project is expected to provide novel insights into central molecular mechanisms within microbial communities. Furthermore, the identification of novel natural products is likely to be an intrinsic part of the proposed research.

链霉菌属细菌由于其非凡的生命周期和其多产的次级代谢而具有重大的科学意义，其产物包括大多数临床处方抗生素。链霉菌的代谢潜力尚未得到充分利用，它们被视为新抗生素的重要来源，可以帮助治疗抗生素耐药性感染。对链霉菌生物学的更全面的理解将允许有效地利用其独特的代谢和发育能力。最近的研究表明，模式生物委内瑞拉链霉菌在面对真菌或营养不良的环境时，可以利用一种新描述的称为探索性生长的生长行为，逃离其经典的生命周期。探索者细胞作为无分支的营养菌丝生长，并且与“正常”营养菌丝相比具有更快的生长速率。有趣的是，探索并不依赖于经典的发育调节因子，这表明它代表了一种新的生长形式。链霉菌的探索为阐明微生物通讯、微生物发育和次生代谢的分子和调控机制提供了一个杰出的系统。基于RNA测序分析和化学诱变，已经证实了几个基因参与探索性生长的调控。此外，已检测到次级代谢物簇的表达改变。利用互补的遗传，生物化学，细胞生物学和代谢分析，拟议的项目将研究探索是如何调节的，特别关注菌落扩张的独特机制，以及探索如何影响次级代谢产物的产生。该项目有望为微生物群落内的中心分子机制提供新的见解。此外，新的天然产物的鉴定很可能是拟议研究的一个内在组成部分。