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

• 批准号: 2325114
• 负责人: Hans Renata
• 金额: $ 67万
• 依托单位: William Marsh Rice University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-06-01 至 2025-03-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2325114&HistoricalAwards=false
• 关键词: CAREER; Chemoenzymatic; Total; Synthesis; Terpenoids

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化学合成项目通过该奖项支持斯克里普斯研究所化学系Hans Renata教授的研究。本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具有多种生物功能的小分子。许多萜类分子只能从天然来源中获得少量。以有效的方式制备它们的实验室方法仍然是一个未解决的挑战。这项研究使用自然界的催化剂，即酶，来修饰起始材料并产生有用的构建模块。然后，构建块被用来制备各种萜类化合物。该研究策略简化了对萜类化合物的获取，有助于进一步研究其生理功能。从事这些研究的学生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。在开展研究活动的同时，Renata教授正在组织外联工作，包括课堂教育和公众参与，以培养年轻学生和当地社区成员对科学的兴趣。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。本项目的目标是建立化学酶方法来获得具有独特结构基序的氧化萜类化合物，特别是具有“trans-trans-trans”，“trans-trans-syn”和“trans-syn-trans”环结的萜类化合物。这是通过结合易于获得的原料萜烯的选择性生物催化氧化和最先进的碳-碳键结构化学方法来实现的。这一领域的研究有助于形成一种新型的合成逻辑（“化学酶逻辑”），用于获取具有有趣结构的复杂分子。为了补充研究活动，还设计了外联工作、新的生物催化课程材料和外部系列讲座，以鼓励年轻学生、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。