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