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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.

在这个奖项从生命过程的化学程序在化学和生物技术，生物化学，生物工程，环境和运输系统部门的生物技术，生物化学和生物质工程计划的部门，博士罗马斯Kazlauskas和安东尼院长，从明尼苏达大学双子城，将复活祖先的通才酶使用基因合成。目标是羟基腈裂解酶的祖先，它催化碳-碳键的形成：氰化物与醛的加成。这项研究将测试这些祖先酶催化其他碳-碳键形成反应的能力，并针对不同的反应进行优化。化学合成中的当前挑战是在使用环境友好的条件和试剂的同时催化地和立体选择性地组装复杂分子。生物催化是一种潜在的解决方案，但目前的生物催化剂的反应范围有限。这项工作构成了一种发现催化非自然反应的生物催化剂的新方法，该方法使用碳-碳键形成反应作为测试案例。对复活的祖先酶的研究试图回答新酶和代谢途径如何进化的基本问题。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额外的化学反应，包括潜在有用的非自然反应。拟议的工作将培训本科生，研究生和博士后学生以化学方法解决跨学科问题，积极招募和吸收化学科学中代表性不足的群体的学生，并支持小学生的外联。