CAREER: Evolutionary Mechanisms for Recruiting Promiscuous Enzyme Activities into New Metabolic Pathways

职业：将混杂的酶活性引入新代谢途径的进化机制

• 批准号: 1253975
• 负责人: Margaret Glasner
• 金额: $ 71.57万
• 依托单位: Texas A&M AgriLife Research
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-03-01 至 2019-02-28
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1253975&HistoricalAwards=false
• 关键词: CAREER; Evolutionary; Mechanisms; Recruiting; Promiscuous

The scientific goal of this project is to discover how and why certain enzymes are capable of evolving new functions. Previous research partially answered the "how" question: in addition to their biological function, many enzymes carry out "promiscuous" side reactions by chance. If a promiscuous activity becomes useful for an organism, natural selection will act to improve that activity. Although many enzymes have promiscuous activities, they might not be equally capable of evolving new functions. In order to identify characteristics that promote evolvability, this research project is comparing the evolution, structure, and function of a family of promiscuous enzymes to their non-promiscuous relatives. Identifying the sequence, structural, and catalytic properties that were required for the evolution of a new function will facilitate the development of new strategies for engineering other enzymes to carry out new activities. Improving protein engineering methodology has numerous applications in industry and medicine, such as using biodegradable enzymes to replace toxic chemicals in industrial processes.Broader ImpactsThis project will support education in the research laboratory and classroom, providing interdisciplinary training in bioinformatics and biochemistry, a major growth area in the biological sciences because of the development of high-throughput DNA sequencing technologies. The participation of under-represented minorities in scientific research will be increased by providing full-time summer internships to undergraduates recruited from colleges that mainly serve minority populations and have limited research opportunities. Active learning will be fostered through the augmentation of a lecture course with a research project that integrates concepts from metabolism with bioinformatics methods developed in the research laboratory. Finally, evolutionary thinking will be introduced into a freshman biochemistry and genetics class, with the goal that these students will become citizens who can explain the mechanisms of evolution and how it impacts their lives.

该项目的科学目标是发现某些酶如何以及为什么能够进化出新的功能。以前的研究部分回答了“如何”的问题：除了它们的生物学功能，许多酶偶然地进行“混杂”的副反应。如果一种混杂的活动对一个生物体变得有用，自然选择就会采取行动来改善这种活动。虽然许多酶具有混杂的活性，但它们可能无法同等地进化出新的功能。为了确定促进进化的特征，该研究项目正在比较一个混杂酶家族与其非混杂亲属的进化，结构和功能。确定新功能进化所需的序列、结构和催化特性，将有助于开发新的策略，以工程化其他酶来执行新的活动。改进蛋白质工程方法在工业和医学中有许多应用，例如在工业过程中使用可生物降解的酶来代替有毒化学品。更广泛的影响这个项目将支持研究实验室和教室的教育，提供生物信息学和生物化学的跨学科培训，这是生物科学的一个主要增长领域，因为高通量DNA测序技术的发展。将通过向从主要为少数群体人口服务、研究机会有限的学院招聘的本科生提供全职暑期实习机会，增加代表性不足的少数群体参与科学研究的机会。积极学习将通过增加一个讲座课程与研究项目，整合从新陈代谢的概念与生物信息学方法在研究实验室开发的促进。最后，进化思想将被引入到新生的生物化学和遗传学课程中，目标是让这些学生成为能够解释进化机制及其如何影响他们生活的公民。