SPECIFICITY IN TERPENE AND STEROL BIOSYNTHESIS

萜烯和甾醇生物合成的特异性

• 批准号: 3268578
• 负责人: ROBERT M. COATES
• 金额: $ 19.95万
• 依托单位: UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
• 依托单位国家: 美国
• 财政年份: 1979
• 资助国家: 美国
• 起止时间: 1979-03-01 至 1988-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3268578
• 关键词: chemical models; cholesterol; cyclization; diterpenes; drug design /synthesis /production; geranyl compound; mass spectrometry; molecular rearrangement; nuclear magnetic resonance spectroscopy; pyrophosphatase; sesquiterpenes; stereochemistry; steroid biosynthesis; sterols; terpenes

Terpenes and sterols manifest a variety of biological functions and activities as hormones, plant regulatory substances, pheromones, antibiotics, and phytoalexins among others. A knowledge of the sterospecificity and mechanisms associated with individual steps in the biosynthetic pathways to them will facilitate the rational design of specific inhibitors or promoters. This research is concerned with elucidating the stereochemistry and/or mechanistic features of key biosynthetic reactions in the formation of kaurene and related polycyclic diterpenes, gibberellic acid, squalene, cholestrol, and dolichol. The biosynthesis of kaurene, beyerene, and trachylobane by soluble enzyme preparations from Marah macrocarpus and Ricinus communis is to be investigated with labelled substrates, substrate analogues, and a new intermediate. The mechanism of squalene biosynthesis will be probed by synthesis and testing of the cyclobutyl isomer of presqualene pyrophosphate. The stereochemistry of the prenylation reaction forming the cis double bonds of dolichol is to be established by use of tritium-labelling. Chiral methyl groups and oxygen-18 labelling will be used to determine the stereochemistry of the methyl hydroxylation reaction which begins the conversion of kaurene to gibberellic acid. A series of 4Alpha-hydroxymethyl, 4Alpha-formyl, and 4Alpha-carboxyl Delta7-sterols proposed as intermediates in cholesterol biosynthesis are to be synthesized and the stereochemistry of the enzymatic hydroxylmethyl-formyl oxidation is to be investigated.

萜烯和固醇表现出多种生物学功能， 作为激素，植物调节物质，信息素的活动， 抗生素，以及植物抗生素等。 对 与单个步骤相关的纯特异性和机制 生物合成途径将促进 特定的抑制剂或启动子。 这项研究与 阐明密钥的立体化学和/或机械特征 Kaurene和相关多环的形成中的生物合成反应 二萜，甘贝尔酸，鳞，胆固醇和多甲醇。 这 可溶性酶的Kaurene，Beyerene和Trachylobane的生物合成 Marah Macrocarpus和Ricinus Communis的准备工作将是 用标记的底物，底物类似物和一个新的 中间的。 鳞状生物合成的机制将由 presqualene的环丁基异构体的合成和测试 焦磷酸盐。 形成原始反应的立体化学 Dolichol的顺式双键将通过使用 标签。 手性甲基和氧气-18标记将是 用于确定甲基羟基化反应的立体化学 这开始了Kaurene转化为Gibberellic Acid。 一系列 4Alpha-羟甲基，4Alpha-formyl和4alpha-carbarboxyl delta7-sterols 胆固醇生物合成中的中间体提议应合成 酶羟基甲基甲酰基氧化的立体化学是 被调查。