BIOSYNTHESIS OF ERGOT ALKALOIDS

麦角生物碱的生物合成

• 批准号: 3299524
• 负责人: HEINZ G FLOSS
• 金额: $ 14.42万
• 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 1992-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3299524
• 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.

具有重要商业价值的麦角生物碱的生物合成， 在一个合成有机和生物有机的合作中研究 研究机构 为了解开C环闭合的机制， 麦角林系统，几种潜在中间体的合成， 将开发二甲基烯丙基色氨酸和裸花雀黄素-I并用于 制备同位素标记的底物。 这些将在喂养中进行测试 用麦角菌培养物进行诱捕实验， 在生物合成中的作用。 在体内证明的转化将 在麦角菌的无细胞提取物中进行检测，关键酶将 进行更详细的机理研究。 除了C环 形成，我们将在酶的水平上，也研究环化的 裸麦角碱-I到农麦角碱。 第二个长期目标是 麦角生物碱进化关系的阐明 利用分子遗传学方法研究真菌和高等植物的生物合成途径 approach.