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FARNESOL OXIDATION IN INSECTS--CHARACTERIZATION

昆虫中金合欢醇的氧化——表征

基本信息

批准号：
2881377
负责人：
STEPHANIE E SEN
金额：
$ 11.19万
依托单位：
INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
依托单位国家：
美国
项目类别：
财政年份：
1999
资助国家：
美国
起止时间：
1999-09-01 至 2002-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/2881377
关键词：
HMG coA reductases Manduca alcohol dehydrogenase alcohols enzyme activity enzyme mechanism enzyme structure farnesyl compound hormone biosynthesis insecticides invertebrate endocrinology juvenile hormones oxidation oxidoreductase inhibitor protein purification

项目摘要

DESCRIPTION (verbatim from the applicant's abstract): Juvenile hormone (JH) is a structurally unique sesquiterpenoid found exclusively in invertebrates and some plants. Since it is well established that precise modulation of JH levels is required for regulating insect growth and development, inhibition of JH biosynthesis can be viewed as a potential method for selectively killing insects. Indeed, compounds that block JH biosynthesis (termed anti-juvenoids) are known and several are of commercial importance. This proposal outlines experiments aimed at understanding a required step in insect juvenile hormone biosynthesis, namely the oxidation of farnesol to farnesal. Very little is known about the enzyme (or enzymes) responsible for farnesol metabolism in insects; however, prior studies indicate that it is a highly substrate-specific process that may be catalyzed by an oxidase, rather than a dehydrogenase. To better characterize farnesol metabolism in insects and to ascertain its suitability for anti-juvenoid development, we will perform the following experiments: i) we will synthesize and test a variety of farnesol analogs, to determine the structural parameters required for activity, ii) we will determine whether more than one enzyme is involved in JH production, specifically as it relates to JH homolog biosynthesis, iii) we will determine what class of oxidative enzyme is involved in farnesol metabolism, iv) we will attempt to purify the enzyme to homogeneity, using traditional chromatographic methods, and v) we will synthesize and test a series of compounds as potential selective inhibitors of farnesol (and JH) metabolism in insects. The information obtained from these studies should be useful in better understanding JH metabolism and may be useful in developing alternative strategies for insect control.

描述(摘自申请者摘要)：保幼激素一种结构独特的倍半萜类化合物，仅见于无脊椎动物和一些植物。因为众所周知，JH电平精确调制是调节昆虫生长发育所必需的，抑制JH 生物合成可以被视为一种潜在的选择性杀戮方法昆虫。事实上，阻止JH生物合成的化合物(称为抗幼虫类化合物) 都是已知的，其中几个具有商业价值。该提案概述了旨在理解以下所需步骤的实验昆虫保幼激素的生物合成，即法尼醇氧化为法尼沙尔。人们对这种酶知之甚少。昆虫中的法尼醇代谢；然而，先前的研究表明，它是一种底物专一性很强的过程，可以由一种酶催化，而不是而不是脱氢酶。为了更好地描述昆虫体内的法尼醇代谢并确定其为了适应反青少年的发展，我们将进行以下工作实验：i)我们将合成和测试各种法尼醇类似物，以确定活动所需的结构参数，ii)我们将确定JH的生产是否涉及一种以上的酶，具体地说，由于它与JH同源生物合成有关，III)我们将确定哪一类氧化酶参与法尼醇的代谢，iv)我们将尝试用传统的层析法将酶纯化为均一种方法，以及v)我们将合成并测试一系列化合物作为潜在的昆虫体内法尼醇(和JH)代谢的选择性抑制剂。从这些研究中获得的信息应该对更好地了解JH代谢，可能有助于开发替代方案防治虫害的策略。