BIOSYNTHESIS OF CYCLOPENTANOIDS

环戊烷类化合物的生物合成

基本信息

批准号：
3274015
负责人：
RONALD J PARRY
金额：
$ 11.51万
依托单位：
RICE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
1978
资助国家：
美国
起止时间：
1978-09-01 至 1992-08-31
项目状态：
已结题

项目摘要

It is proposed to continue investigations of the biosynthesis of three novel, naturally occurring cyclopentanoid compounds. These are the alkaloid sesbanine, which occurs in the leguminous plant Sesbania drummondii, the nucleoside antibiotic aristeromycin, which is produced by Streptomyces citricolor, and the phytotoxin coronatine, which is isolated from Pseudomonas syringae. Previous studies have revealed that sesbanine is derived from nicotinic acid and shikimic acid with the possible intermediacy of p-hydroxybenzoic acid. The goal of future studies will be to verify that p-hydroxybenzoic acid is a specific precursor of sesbanine and to examine the mechanism of the conversion of the aromatic ring of this compound into the cyclopentane ring of sesbanine. Prior investigations of aristeromycin biosynthesis have shown that the adenine ring of the antibiotic is biosynthesized along familiar lines while the cyclopentane ring of the antibiotic is derived from D-glucose. Some clues to the mechanism of the ring closure were obtained by means of incorporation experiments with specifically tritiated forms of glucose. In the future, the studies with specifically tritiated forms of glucose will be completed and efforts will then be focused on elucidating the nature of some of the intermediates involved in the formation of the cyclopentane ring. These latter investigations will utilize precursor incorporation experiments, cell-free extracts, and mutants. Initial investigations of coronatine have demonstrated that the hydrindane portion of the molecule, coronofacic acid, is a novel polyketide derived from five acetate units and one pyruvate unit, with the latter serving as the starter unit. The cyclopropyl amino acid moiety of the toxin, coronamic acid, has been found to be biosynthesized from L-alloisoleucine. Future investigations of coronatine bio- synthesis will employ precursor incorporation experiments to probe both the mechanism of assembly of the polyketide and the mechanism of cyclopropane ring formation.

建议继续研究三种新颖的，天然存在的环戊酸化合物。这些是生物碱塞巴宁，发生在豆类植物Sesbania drummondii，核苷抗生素芳香霉素，由柠檬色链霉菌产生，从假单胞菌分离出的植物毒素冠状动脉蛋白丁香。先前的研究表明塞斯巴因是衍生的从烟酸和shikimic Acid中 p-羟基苯甲酸的中介。未来的目标研究将是验证p-羟基苯甲酸是一种特定的塞巴金的先驱，并检查该化合物的芳香环转换为塞斯巴蛋白的环戊烷环。事先调查瘤霉素生物合成表明抗生素是按熟悉的线生物合成的，而抗生素的环烷环衍生自D-葡萄糖。通过与特定曲折的合并实验的手段葡萄糖的形式。将来，研究专门葡萄糖的曲折形式将完成，然后将努力专注于阐明某些中间体的性质参与了环戊烷环的形成。这些后者调查将利用前体掺入实验，无细胞提取物和突变体。初步调查冠状定冠素证明了该冠状的部分分子，冠状酸，是一种源自五个乙酸盐单元和一个丙酮酸单元，后者供应作为起动单元。环丙基氨基酸部分毒素，冠状酸已被发现是从生物合成的 l-抗甲甲苯磺酸氨酸盐。未来对冠状动脉生物的调查合成将采用前体掺入实验探测聚酮化合物和聚酮的组装机制和环丙烷环形成的机理。