Investigating Microbial Natural Product Biosynthesis

研究微生物天然产物的生物合成

• 批准号: 412793-2013
• 负责人: Horsman, Geoffrey
• 金额: $ 2.55万
• 依托单位: Wilfrid Laurier University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2016
• 资助国家: 加拿大
• 起止时间: 2016-01-01 至 2017-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=596178
• 关键词: Investigating; Microbial; Natural; Product; Biosynthesis

Microorganisms occupy every habitat on earth and possess an astounding array of metabolic diversity. This metabolic power is used in Nature to drive biogeochemical cycles, and has been harnessed by humans for green chemistry, bioremediation, and the production of chemicals such as antibiotics. Although the crucial role of microbes in the environment and human health is increasingly apparent, characterizing and exploiting their full potential has long been limited by our inability to culture them. Indeed, less than 1% of microorganisms may be grown in laboratory culture, indicating that a vast reservoir of microbial metabolic diversity remains untapped. Isolating total DNA from an environmental sample and expressing these genes in a cultivable bacterial host (metagenomics) can capture this reservoir and provide access to previously unknown microbial enzymes and small molecules with potential to address societal challenges in human health, energy, agriculture, and the environment. Among such challenges, discovering new bioactive organophosphorus compounds is an important goal that can be realized by understanding microbial strategies of phosphonate biosynthesis. The long-term objective of the proposed research program is to discover novel small molecules and biosynthetic enzymes encoded by uncultivated microorganisms. The immediate goals of the proposed research are to discover C-P bond-containing small molecules (phosphonates/phosphinates) and characterize the enzymes involved in their biosynthesis. Phosphonates are small molecule natural products used as herbicides and antibiotics, but relatively few natural phosphonates are known. The proposed research aims to identify novel phosphonates with potential applications in agriculture and medicine, and uncover new enzymes capable of being exploited for biocatalysis and green chemistry applications.

微生物占据了地球上的每个栖息地，并具有令人惊讶的代谢多样性。这种代谢能力在本质上被用来驱动生物地球化学周期，并由人类利用绿色化学，生物修复和抗生素等化学物质的产生。尽管微生物在环境和人类健康中的关键作用越来越明显，但表征和利用其全部潜力的表征一直受到我们无法培养它们的限制。实际上，在实验室培养中可能会生长不到1％的微生物，这表明大量的微生物代谢多样性仍然未开发。从环境样品中分离总DNA并在可栽培的细菌宿主（元基因组学）中表达这些基因可以捕获该储层，并提供对以前未知的微生物酶和小分子的访问，该酶有潜在地应对人类健康，能源，农业和环境中社会挑战的潜力。在此类挑战中，发现新的生物活性有机磷化合物是一个重要的目标，可以通过了解磷酸化生物合成的微生物策略来实现。拟议的研究计划的长期目标是发现由未培养的微生物编码的新型小分子和生物合成酶。拟议的研究的直接目标是发现含C键的小分子（磷酸盐/磷酸盐），并表征与其生物合成有关的酶。磷酸盐是用作除草剂和抗生素的小分子天然产物，但已知的天然磷酸盐相对较少。拟议的研究旨在鉴定具有农业和医学潜在应用的新型磷酸盐，并发现能够利用生物催化和绿色化学应用的新酶。