CAREER: Chemoenzymatic Total Synthesis of Terpenoids via P450 Catalysis

职业：通过 P450 催化化学酶法全合成萜类化合物

基本信息

批准号：
2228369
负责人：
Hans Renata
金额：
$ 67万
依托单位：
University of Florida
依托单位国家：
美国
项目类别：
Continuing Grant
财政年份：
2022
资助国家：
美国
起止时间：
2022-06-01 至 2023-04-30
项目状态：
已结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=2228369&HistoricalAwards=false
关键词：
CAREER Chemoenzymatic Total Synthesis Terpenoids

项目摘要

With this Award, the Chemical Synthesis Program of the NSF Division of Chemistry is supporting the research of Professor Hans Renata in the Department of Chemistry at The Scripps Research Institute. This research develops new strategies for the synthesis of terpenoids, naturally occurring small molecules that have a variety of biological functions. Many of these terpenoid molecules can only be obtained in small quantities from natural sources. Laboratory methods to prepare them in an efficient manner still remain an unsolved challenge. The research uses nature’s catalysts, i.e. enzymes, to modify starting materials and produce useful building blocks. The building blocks are then used to prepare a wide range of terpenoids. Streamlined access to terpenoids enabled by this research strategies helps support further studies on their physiological functions. Students working on these studies receive important training in chemical and biological sciences to support their future careers in science and engineering. Concomitant with the research activities, the Professor Renata is organizing outreach efforts including classroom education and public engagement to cultivate interest in science among young students and members of the local community.The Renata lab aims to develop novel strategies to access important natural products by incorporating biocatalytic transformations. The goal of this project is to establish chemoenzymatic means to access oxidized terpenoids with unique structural motifs, specifically terpenoids bearing “trans-trans-trans”, “trans-trans-syn” and “trans-syn-trans” ring junctions. This is achieved by combining site-selective biocatalytic oxidation of readily available feedstock terpenes and state-of-the-art chemical methodologies for carbon-carbon bond constructions. Studies in this area help formulate a new type of synthetic logic (“chemoenzymatic logic”) for accessing complex molecules with interesting architectures. To complement the research activities, outreach efforts, new coursework material in biocatalysis, and an external lecture series are designed to encourage participation in science among young students, underrepresented groups and members of the local community.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.

美国国家科学基金会化学部的化学合成项目正在支持斯克里普斯研究所化学系汉斯·雷纳塔教授的研究，该研究开发了合成萜类化合物的新策略，萜类化合物是天然存在的小分子。许多这些萜类化合物只能从天然来源中少量获得，而利用自然界的催化剂进行有效制备仍然是一个未解决的挑战。即酶，以修改起始材料并产生有用的结构单元，然后使用该结构单元来制备各种萜类化合物，通过该研究策略简化对萜类化合物的获取，有助于支持从事这些研究的学生的进一步研究。接受化学和生物科学方面的重要培训，以支持他们未来在科学和工程领域的职业生涯，雷纳塔教授正在组织外展活动，包括课堂教育和公众参与，以培养年轻学生和成员对科学的兴趣。 Renata 实验室旨在通过结合生物催化转化来开发获取重要天然产物的新策略。该项目的目标是建立化学酶方法来获取具有独特结构基序的氧化萜类化合物，特别是带有“反式-反式-反式”的萜类化合物。 ”、“反式-反式-顺式”和“反式-反式-反式”环连接是通过结合现成原料的位点选择性生物催化氧化来实现的。该领域的研究有助于制定一种新型合成逻辑（“化学酶逻辑”），用于获取具有有趣结构的复杂分子，以补充研究活动。外展活动、生物催化方面的新课程材料工作以及外部讲座系列旨在鼓励年轻学生、代表性不足的群体和当地社区成员参与科学。该奖项反映了 NSF 的法定使命，并被认为值得支持通过使用基金会的智力优点和更广泛的影响审查标准进行评估。