CYP701A: A Family of Multifunctional Plant Cytochromes P450 in Terpenoid Biosynthesis

CYP701A：萜类生物合成中的多功能植物细胞色素 P450 家族

• 批准号: 0416948
• 负责人: Reuben Peters
• 金额: --
• 依托单位: Iowa State University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-01 至 2010-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0416948&HistoricalAwards=false
• 关键词: CYP701A; Family; Multifunctional; Plant; Cytochromes

Terpenoids, which form the largest family of natural products, have extensive biological and industrial functions. The majority of terpenoids, indeed of all natural products, are exclusively produced by plants. As a consequence of such metabolic prowess, plants encode more cytochromes P450 (P450s) than other organisms. These monooxygenases catalyze key steps in the biosynthesis and detoxification of many metabolites. Despite their importance in the production of valuable natural products, little mechanistic work has been carried out with plant derived P450s. This project targets the CYP701A family of P450s, which is largely composed of kaurene oxidase from various species. Kaurene oxidase is a universal plant P450 catalyzing three consecutive reactions in diterpenoid gibberellin plant growth hormone biosynthesis. In addition, related functions have been ascribed to the group of CYP701A P450s found in rice. Thus, functional characterization of the individual enzymes within this group of homologous P450s will create a model system for investigating the enzymatic basis for differential function, leading to clarification of the structure/function basis for the substrate selectivity and catalytic activity of these plant cytochromes P450. Broader Impact: In the course of investigating these microsomal P450s, the undergraduate and graduate students involved in this research project will receive broad training in the critical area of membrane biochemistry. The students also will be trained in functional genomics approaches, as extensive sequence information is now becoming available for plant species. Further, the techniques, strategies, and knowledge generated by this project will enhance teaching, not only at the university level, but also efforts targeted at primary and secondary school teachers. Thus, the knowledge generated by this project will be widely disseminated, both through the scientific literature, as well as broad educational efforts. Finally, these studies may have some commercial impact due to the importance of plant P450s in the biosynthesis of valuable natural product metabolites and their potential uses in industrial processes.

萜类化合物是最大的天然产物家族，具有广泛的生物学和工业功能。大多数萜类化合物，实际上是所有天然产物，都是由植物产生的。由于这种强大的代谢能力，植物比其他生物体编码更多的细胞色素 P450 (P450s)。这些单加氧酶催化许多代谢物的生物合成和解毒的关键步骤。尽管植物源性 P450 在生产有价值的天然产品中很重要，但人们对其进行的机械工作却很少。该项目针对 P450 的 CYP701A 家族，该家族主要由来自不同物种的贝壳杉烯氧化酶组成。贝壳杉烯氧化酶是一种通用植物 P450，催化二萜类赤霉素植物生长激素生物合成中的三个连续反应。此外，相关功能已归因于水稻中发现的 CYP701A P450 组。因此，这组同源 P450 中各个酶的功能表征将创建一个模型系统，用于研究差异功能的酶学基础，从而澄清这些植物细胞色素 P450 的底物选择性和催化活性的结构/功能基础。更广泛的影响：在研究这些微粒体 P450 的过程中，参与该研究项目的本科生和研究生将接受膜生物化学关键领域的广泛培训。学生们还将接受功能基因组学方法的培训，因为现在可以获取植物物种的广泛序列信息。此外，该项目产生的技术、策略和知识将增强教学，不仅在大学层面，而且还针对中小学教师。因此，该项目产生的知识将通过科学文献以及广泛的教育工作得到广泛传播。最后，由于植物 P450 在有价值的天然产物代谢物的生物合成中的重要性及其在工业过程中的潜在用途，这些研究可能会产生一些商业影响。