BIOSYNTHESIS OF ERGOT ALKALOIDS

麦角生物碱的生物合成

• 批准号: 3299525
• 负责人: HEINZ G FLOSS
• 金额: $ 15.13万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 1989
• 资助国家: 美国
• 起止时间: 1989-04-01 至 1993-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3299525
• 关键词: aminoacid biosynthesis; bromocriptine; catalyst; drug design /synthesis /production; drug screening /evaluation; enzyme mechanism; ergolines; messenger RNA; molecular cloning; oxytocics; plant extracts; radiotracer; tissue /cell culture; tryptophan

The biosynthesis of the commercially important ergot alkaloids will be studied in a collaboration between a synthetic organic and a bioorganic research group. To unravel the mechanism of the closure of ring C of the ergoline system, syntheses for several potential intermediates between dimethylallytryptophan and chanoclavine-I will be developed and used to prepare isotopically labeled substrates. These will be tested in feeding and trapping experiments with cultures of the ergot fungus to establish their role in the biosynthesis. Conversions demonstrated in vivo will then be examined in cell-free extracts of the ergot fungus, and key enzymes will be purified for more detailed mechanistic studies. In addition to C-ring formation we will, at the enzymatic level, also study the cyclization of chanoclavine-I to agroclavine. A second, long-term goal of this project is the elucidation of the evolutionary relationship of the ergot alkaloid biosynthetic pathways in fungi and higher plants using a molecular genetic approach.

对具有重要商业价值的麦角生物碱进行生物合成