Connecting social interactions to natural product biosynthesis in actinomycete bacteria

将社交互动与放线菌天然产物生物合成联系起来

• 批准号: 10224240
• 负责人: Matthew F Traxler
• 金额: $ 31.92万
• 依托单位: UNIVERSITY OF CALIFORNIA BERKELEY
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-08-01 至 2023-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10224240
• 关键词: Actinobacteria class; Anabolism; Antibiotics; Antifungal Agents; Antineoplastic Agents; Bacteria; Bacterial Infections; Cells; Chemicals; Clinical; Communication; Cues; Devices; Foundations; Future; GTP-Binding Proteins; Gene Expression; Genetic; Goals; Knowledge; Lead; Microbe; Microfluidic Microchips; Modeling; Molecular; Natural Products; Production; Regulation; Research; Resistance; Running; Signal Transduction; Social Interaction; Source; Specificity; Speed; Streptomyces coelicolor; System; Work; anti-cancer; insight; microbial; microorganism interaction; pathogen; protein activation; social

PROJECT SUMMARY/ABSTRACT Natural products from bacteria have long been the frontline defense in the struggle against bacterial infections, and have also found wide use as antifungals, anthelminthics, anti-cancer drugs, and immunosupressants. One group of bacteria, the actinomycetes, has historically been the deepest source of clinically-useful natural products. Recent work has demonstrated that natural product biosynthesis often results from microbial communication in the form of interactions between cells in colonies of a single actinomycete, or by interactions with microbes of different species. Together, these observations underscore the idea that induction of natural product biosynthesis is socially-driven. The goal of this study is to understand how inter- and intra- species interactions activate natural product biosynthesis at a molecular level. Our first research objective seeks a mechanistic understanding of how a model actinomycete, Streptomyces coelicolor, activates expression of genes for natural product biosynthesis in the presence of other actinomycetes. We have found that this activation requires an unusual and poorly-understood signal transduction mechanism found in actinomycetes that shares parallels with eukaryotic systems that rely on G protein activation. Our second research objective seeks a systems-level understanding of natural product biosynthesis in S. coelicolor within the context of cell fate decisions. Knowledge generated from this objective may be employed to someday manipulate cell fates within actinomycete cultures to drive natural products discovery and production. These objectives run in parallel with our efforts to build a microfluidic device for studying microbial interspecies interactions with unprecedented speed, throughput, and specificity. This device will have multiple applications related to our first two objectives and beyond. This research will illuminate the social aspect of natural product biosynthesis, and in the long term, provide a foundation for harnessing microbial social cues and genetic regulation to maximize future natural products discovery efforts. !

项目总结/文摘