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.

该奖项是根据2021年《美国救援计划法》（公共法第117-2）的全部资助。在化学分校的化学合成计划（SYN）计划的支持下，加利福尼亚 - 圣塔芭芭拉分校（UCSB）的杨Yang Yang Yang Yang Yang Yang Yang Yang Yang Yang Yang Yang Yang Yang Yang Yang Yang Yang Yang Yang Yang Yang Yang Yang Yang santa Barbara（UCSB）正在与一支研究生和本科生一起发现和开发BioCatalyStsssssssssssssssssssssc-alltallation c-alkallation contions。酶是蛋白质的生物催化剂，自然发展为催化化学反应，通常具有出色的化学，区域和立体选择性。这些生物催化剂在异常温和的条件下在水中起作用，从而使化学合成以更可持续的方式进行。此外，酶很容易使用微生物宿主大规模生产，并最近被利用用于化学制造和法胺工艺化学的应用。希望发现并设计新的生物催化剂类别，以提高效率和选择性催化合成的反应。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，以调查并发现有效的新型生物催化剂，以实现选择性C烷基化反应，α-至carbonyl群，这一过程被广泛用于有机化合物的合成中。与UCSB的正在进行的外展计划合作，杨博士将领导动手研讨会，向当地的7至12年级学生介绍化学合成和生物催化的关键概念和应用。COMBINGYANG及其学生的基因组挖掘和蛋白质工程学的思想和技术培养Yang博士及其学生，Yang博士和他的学生旨在探究和反应性地反应良好的研究。尽管这些转化具有合成的效用，除了使用有机立体分析的示例外，与羰基相邻的C-烷基化的一般催化不对称方法相对较少。为了应对这一挑战，杨博士和他的小组正在开发一个由一组工程烷基转移酶组成的完全生物催化平台，以使用丰富且易于可用的烷基化试剂来促进高度立体选择性烷基化工艺。该生物催化烷基化平台曾经充分开发，预计将使一系列有用的手性构件方便地合成。这项努力的更广泛影响包括从代表性不足的群体到科学，技术，工程和数学（STEM）职业的动手接触，以及在地方一级和服务不足的社区的计划外展活动。该奖项反映了NSF的法定任务，并通过评估基金会的范围进行了评估和宽广的范围，并已被认为是基金会的范围。