New enzyme-catalyzed reactions from catalytically promiscuous ancestral enzymes

来自催化混杂祖先酶的新酶催化反应

基本信息

批准号：
1152804
负责人：
Romas Kazlauskas
金额：
$ 32.98万
依托单位：
University of Minnesota-Twin Cities
依托单位国家：
美国
项目类别：
Standard Grant
财政年份：
2012
资助国家：
美国
起止时间：
2012-09-01 至 2015-08-31
项目状态：
已结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=1152804&HistoricalAwards=false
关键词：
New enzyme catalyzed reactions catalytically

项目摘要

In this award from the Chemistry of Life Processes Program in the Division of Chemistry and the Biotechnology, Biochemical, and Biomass Engineering Program in the Chemical, Bioengineering, Environmental, and Transport Systems Division, Drs. Romas Kazlauskas and Antony Dean, from the University of Minnesota, Twin Cities, will resurrect ancestral generalist enzymes using gene synthesis. The targets are ancestors of hydroxynitrile lyases, which catalyze a carbon-carbon bond formation: addition of cyanide to aldehydes. The research will test the ability of these ancestral enzymes to catalyze other carbon-carbon bond forming reactions and optimize them for different reactions. A current challenge in chemical synthesis is to assemble complex molecules catalytically, and stereoselectively while using environmentally friendly conditions and reagents. Biocatalysis is a potential solution, but the reaction range of current biocatalysts is limited. This work constitutes a new approach to discover biocatalysts that catalyze unnatural reactions, which uses carbon-carbon bond forming reactions as a test case. Studies of resurrected ancestral enzymes seek to answer basic questions of how new enzymes and metabolic pathways evolve. In addition, resurrected ancestral enzymes may be starting points for engineering new enzymes because ancestral enzymes can catalyze additional chemical reactions, including potentially useful unnatural reactions. The proposed work will train under-graduate, graduate and postdoctoral students in a chemical approach to solving interdisciplinary problems, actively recruit and include students from groups underrepresented in chemical sci-ences, and support outreach to elementary school students.

在化学过程中的化学过程和生物技术，生物化学和生物量工程计划中，化学，生物工程，环境和运输系统部的生物技术和生物量工程计划的奖项。来自明尼苏达大学双城的Romas Kazlauskas和Antony Dean将使用基因合成复活祖先的通才酶。靶标是羟基硝基裂解酶的祖先，它们催化形成碳碳键：将氰化物添加到醛中。该研究将测试这些祖先酶催化其他碳碳键形成反应的能力，并将其优化为不同的反应。化学合成的当前挑战是在使用环保条件和试剂的同时催化复杂的分子和立体选择。生物催化是一种潜在的解决方案，但是电流生物催化剂的反应范围有限。这项工作构成了一种新的方法来发现催化不自然反应的生物催化剂，该反应使用碳碳键形成反应作为测试案例。复活的祖先酶的研究试图回答有关新酶和代谢途径如何发展的基本问题。此外，复活的祖先酶可能是工程新酶的起点，因为祖先酶可以催化其他化学反应，包括潜在有用的非天然反应。拟议的工作将以化学方法来解决跨学科问题，积极招募，并包括来自化学学科中代表性不足的学生，并支持向小学生提供外展活动的学生。