Alkaloid Biosynthetic Studies

生物碱生物合成研究

• 批准号: 10797829
• 负责人: Pinghua Liu
• 金额: $ 13.63万
• 依托单位: BOSTON UNIVERSITY (CHARLES RIVER CAMPUS)
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-01 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10797829
• 关键词: Aging; Alkaloids; Anabolism; Anti-Infective Agents; Biological; Disease; Distal; Enzymes; Epoxy Compounds; Genome; Gold; Iron; Mining; Modeling; Natural Products; Reaction; Sulfhydryl Compounds; Work; anti-cancer; chemical synthesis; dehydrogenation; enzyme activity; functional group; novel; unnatural amino acids

Project Summary / Abstract Alkaloid biosynthetic studies C-H activation is one of the key strategies to introduce structural and functional diversities into natural products in both chemical synthesis and biosynthesis. Non-heme iron enzymes are one of the key classes of C-H activating enzymes. In this work, we will conduct mechanistic studies of several non-hydroxylation reactions catalyzed by non-heme iron enzymes, including endoperoxidation, epoxidation, dehydrogenation, and oxidative C-S bond formation. These functional groups are key to the biological activities of many natural products. In Aim 1, we focus on the distal type of -ketoglutarate dependent non-heme iron enzymes because this is a relatively unexplored class of enzymes. There are two mechanistic models in explaining the activities of these enzymes and we will examine them using carefully selected enzymes (FtmOx1, CnsJ, and PhyH). In Aim 2, we will conduct mechanistic studies on non-heme iron enzymes in ergothioneine and ovothiol biosynthesis. There are two mechanistic models proposed based on theoretical calculations. In this aim, using unnatural amino acid containing enzymes, we will differentiate between the two models.

项目摘要 /摘要 生物类生物合成研究 C-H激活是将结构和功能多样性引入自然的关键策略之一 非血红素铁酶是关键类别之一 C-H激活酶。在这项工作中，我们将对几种非羟基化进行机械研究 由非血红素铁酶催化的反应，包括内氧化，环氧化，脱氢， 和氧化C-S键的形成。这些官能团是许多自然生物学活动的关键 产品。 在AIM 1中，我们专注于远端类型的-酮戊二酸依赖性非血红素铁酶，因为这是 相对意外的酶类。有两个机械模型在解释活动 这些酶，我们将使用精心选择的酶（FTMOX1，CNSJ和PHYH）检查它们。 AIM 2，我们将对甲氨酸和卵菌素中非血红素铁酶进行机械研究 生物合成。基于理论计算提出了两个机械模型。在这个目标中，使用 含有酶的非天然氨基酸，我们将区分这两种模型。

项目成果

Correspondence on "Structural Insight into the Catalytic Mechanism of the Endoperoxide Synthase FtmOx1".

• DOI: 10.1002/anie.202218643
• 发表时间: 2023-09-11
• 期刊: ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
• 影响因子: 16.6
• 作者: Zhang, Lixin;Liu, Xueting;Wang, Xinye;Zhu, Guoliang;Song, Heng;Cheng, Ronghai;Naowarojna, Nathchar;Costello, Catherine E. E.;Liu, Pinghua
• 通讯作者: Liu, Pinghua