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

链霉菌由于其特殊的生命周期和丰富的次级代谢而具有重要的科学意义，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被充分利用，它们被视为有助于治疗抗生素耐药感染的新抗生素的重要来源。更全面的了解链霉菌生物学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，可以使用一种新描述的称为探索性生长的生长行为，从其经典的生命周期中逃脱。探索者细胞以无分枝营养菌丝的形式生长，与“正常”营养菌丝相比，其生长速度要快得多。有趣的是，探索并不依赖于传统的发育调节，这表明它代表了一种新的增长形式。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优秀的系统。基于rna测序分析和化学诱变，已经证实了几个基因参与了探索性生长的调控。此外，还发现了次级代谢物簇的表达改变。利用互补的遗传、生化、细胞生物学和代谢分析，拟议的项目将研究如何调节探索，特别关注菌落扩张的独特机制，以及探索如何影响次生代谢物的产生。该项目有望为微生物群落的核心分子机制提供新的见解。此外，鉴定新的天然产物可能是拟议研究的一个固有部分。

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.