Connecting specialized metabolism to social cues in actinomycete bacteria

将放线菌的特殊代谢与社交线索联系起来

基本信息

批准号：
10623771
负责人：
Matthew F Traxler
金额：
$ 37.96万
依托单位：
UNIVERSITY OF CALIFORNIA BERKELEY
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-08-01 至 2028-05-31
项目状态：
未结题

项目摘要

PROJECT SUMMARY/ABSTRACT Natural products from bacteria continue to be 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. Over the last decade, numerous reports have demonstrated that natural product biosynthesis often occurs in the context of actinomycete interactions. These include interactions between microbes of different species, and cell-cell coordination within colonies of single actinomycetes. Together, these findings have solidified the idea that induction of natural product biosynthesis is socially driven in these bacteria. Despite the importance of this social aspect, how these interactions unfold at the molecular level and how interactions may best be harnessed for natural products discovery remain open questions. The goals of this study are to understand how inter- and intra- species interactions activate natural product biosynthesis at the molecular and systems levels, and to build framework for translating these insights into natural product discovery. First, this work will examine how the model actinomycete Streptomyces coelicolor activates expression of genes for antibiotic production in the presence of other actinomycetes. 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. Second, this work seeks a systems- level understanding of spatially coordinated antibiotic production within individual S. coelicolor colonies. Knowledge generated from this objective may be employed to someday manipulate cell fates within actinomycete cultures to drive natural products discovery and production. Third, this work leverages actinomycete interactions for the discovery of novel natural products. This research serves as a testbed for putting our knowledge of actinomycete interactions into practice, with an emphasis on discovery of compounds with unusual mechanisms of action. In its entirety, this work will illuminate the social drivers 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.

项目摘要/摘要来自细菌的天然产品继续成为与之斗争的一线防御细菌感染，还发现广泛用作抗真菌剂，驱虫药，抗癌毒品和免疫服。一组细菌（放线菌）一直是临床可用性天然产品的最深来源。在过去的十年中，许多报告已经证明天然产物生物合成通常发生在放线菌的背景下互动。这些包括不同物种的微生物和细胞细胞之间的相互作用单个放线菌的菌落中的协调。这些发现共同巩固了自然产物生物合成的诱导是在这些细菌中社会驱动的。尽管这一社会方面的重要性，这些相互作用如何在分子层面上展开以及最好如何利用自然产品发现的互动仍然是开放的问题。这项研究的目标是了解间相互作用如何激活分子和系统水平的天然产品生物合成，并为将这些见解转化为自然产品发现。首先，这项工作将研究如何模型放线菌链霉菌Coelicolor激活基因的抗生素基因表达在其他放线菌的存在下产生。这种激活需要不寻常的，并且在放线菌中发现的信号转导机制不足，该机制具有相似之处依赖于G蛋白激活的真核系统。其次，这项工作寻求一个系统 - 对单个Coelicolor内空间协调的抗生素产生的水平了解殖民地。从这个目标产生的知识可能被用来有一天操纵放线菌培养物中的细胞命运，以推动天然产物的发现和生产。第三，这项工作利用放线菌的相互作用来发现新型天然产物。这研究是将我们对放线菌相互作用的了解的测试台实践，重点是发现具有异常作用机制的化合物。在整个工作，这项工作将阐明自然产品生物合成的社会驱动力，并在长期，为利用微生物社会提示和遗传调节提供了基础最大化未来的天然产品发现工作。

项目成果

期刊论文数量（6）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

The cvn8 Conservon System Is a Global Regulator of Specialized Metabolism in Streptomyces coelicolor during Interspecies Interactions.

DOI：
10.1128/msystems.00281-21
发表时间：
2021-10-26
期刊：
mSystems
影响因子：
6.4
作者：
Bonet B;Ra Y;Cantu Morin LM;Soto Bustos J;Livny J;Traxler MF
通讯作者：
Traxler MF

Genetic Network Architecture and Environmental Cues Drive Spatial Organization of Phenotypic Division of Labor in Streptomyces coelicolor.

DOI：
10.1128/mbio.00794-21
发表时间：
2021-05-18
期刊：
mBio
影响因子：
6.4
作者：
Zacharia VM;Ra Y;Sue C;Alcala E;Reaso JN;Ruzin SE;Traxler MF
通讯作者：
Traxler MF

Multiple lineages of Streptomyces produce antimicrobials within passalid beetle galleries across eastern North America.

DOI：
10.7554/elife.65091
发表时间：
2021-05-04
期刊：
eLife
影响因子：
7.7
作者：
Pessotti RC;Hansen BL;Reaso JN;Ceja-Navarro JA;El-Hifnawi L;Brodie EL;Traxler MF
通讯作者：
Traxler MF

Harnessing Rare Actinomycete Interactions and Intrinsic Antimicrobial Resistance Enables Discovery of an Unusual Metabolic Inhibitor.