CAREER: Engineered SAM-Dependent Enzymes for Stereoselective Alkylation Reactions

职业：用于立体选择性烷基化反应的工程 SAM 依赖性酶

• 批准号: 2145749
• 负责人: Yang Yang
• 金额: $ 69万
• 依托单位: University of California-Santa Barbara
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-02-01 至 2027-01-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2145749&HistoricalAwards=false
• 关键词: CAREER; Engineered; SAM; Dependent; Enzymes

This award is funded in whole under the American Rescue Plan Act of 2021 (Public Law 117-2).With the support of the Chemical Synthesis (SYN) program in the Division of Chemistry, Yang Yang of the University of California-Santa Barbara (UCSB) is working with a team of graduate and undergraduate students to discover and develop biocatalysts for selective C-alkylation reactions. Enzymes are protein biocatalysts that have naturally evolved to catalyze chemical reactions, often with excellent chemo-, regio- and stereoselectivities. These biocatalysts function in water under exceptionally mild conditions, thus allowing chemical synthesis to be carried out in a more sustainable fashion. Furthermore, enzymes are easily produced on a large scale using microbial hosts and have been exploited recently for applications in chemical manufacturing and pharameutical process chemistry. It is desirable to discover and engineer new classes of biocatalysts to catalyze synthetically significant reactions with enhanced efficiency and selectivity. Dr. Yang and his students will exploit their abilities in organic synthesis, physical organic chemistry, enzymology and protein engineering to investigate and discover efficient new biocatalysts for selective C-alkylation reactions, alpha-to a carbonyl group, a process that is widely used in the synthesis of organic compounds. In partnership with ongoing outreach programs at UCSB, Dr. Yang will lead hands-on workshops to introduce local 7-12th grade students to the key concepts and applications of chemical synthesis and biocatalysis.Combining ideas and technologies from organic chemistry, genome mining and protein engineering, Dr. Yang and his students aim to discover and develop new biocatalysts to facilitate selective alkylation reactions. Despite the synthetic utility to these transformation, aside from examples using organocatalysis, there are relatively few general catalytic asymmetric methods for C-alkylation adjacent to a carbonyl group. To address this challenge, Dr. Yang and his group are developing a fully biocatalytic platform consisting of a set of engineered alkyl transfer enzymes to facilitate highly stereoselective alkylation processes using abundant and readily available alkylation reagents. This biocatalytic alkylation platform, once fully developed, is expected to allow for a range of useful chiral building blocks to be synthesized conveniently. Broader impacts of this endeavor include the hands-on exposure of students from underrepresented groups to science, technology, engineering, and mathematics (STEM) careers, as well as planned outreach focused at the local level and on underserved communities.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

该奖项全部由《2021年美国救援计划法案》（公法117-2）资助。在化学系化学合成（SYN）项目的支持下，加州大学圣巴巴拉分校（UCSB）的杨洋正在与研究生和本科生组成的团队合作，发现和开发用于选择性c -烷基化反应的生物催化剂。酶是蛋白质的生物催化剂，自然进化为催化化学反应，通常具有优异的化学选择性、区域选择性和立体选择性。这些生物催化剂在异常温和的条件下在水中发挥作用，从而使化学合成以更可持续的方式进行。此外，酶很容易在微生物宿主上大规模生产，并且最近已被开发用于化学制造和制药过程化学。人们希望发现和设计新型的生物催化剂，以提高效率和选择性来催化重要的合成反应。杨博士和他的学生将利用他们在有机合成、物理有机化学、酶学和蛋白质工程方面的能力，研究和发现高效的新型生物催化剂，用于选择性c -烷基化反应，α -到羰基，这一过程广泛用于有机化合物的合成。杨博士将与加州大学圣迭戈分校的外展项目合作，领导动手研讨会，向当地7-12年级的学生介绍化学合成和生物催化的关键概念和应用。结合有机化学，基因组挖掘和蛋白质工程的思想和技术，杨博士和他的学生旨在发现和开发新的生物催化剂，以促进选择性烷基化反应。尽管这些转化在合成上有实用价值，但除了使用有机催化的例子外，对于邻羰基的c -烷基化，一般的催化不对称方法相对较少。为了应对这一挑战，杨博士和他的团队正在开发一个由一套工程烷基转移酶组成的全生物催化平台，以促进高度立体选择性的烷基化过程，使用丰富且容易获得的烷基化试剂。这种生物催化烷基化平台，一旦完全开发，预计将允许一系列有用的手性构建块被方便地合成。这一努力的更广泛影响包括让代表性不足的群体的学生亲身接触科学、技术、工程和数学（STEM）职业，以及计划在地方一级和服务不足的社区开展外展活动。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。