Elucidating the elaboration of plant diterpenoid natural products

阐明植物二萜天然产物的精制

• 批准号: 8825301
• 负责人: REUBEN JOHN PETERS
• 金额: $ 28.79万
• 依托单位: IOWA STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-08-05 至 2019-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8825301
• 关键词: Agrochemicals; Anabolism; Antibiotics; Area; Biochemical Pathway; Biological; Biological Factors; Biological Models; Chinese People; Clinical Trials; Complex; Diterpenes; Engineering; Environment; Enzymes; Euphorbiaceae; Gene Cluster; Genome; Ginkgo biloba; Goals; Health; Human; Individual; Investigation; Jatropha; Lead; Libraries; Mediating; Medicinal Herbs; Medicinal Plants; Medicine; Metabolic Pathway; Metabolism; Organism; Pathway interactions; Pharmacologic Substance; Phorbol Esters; Physiological; Plants; Production; Research; Resistance; Rice; Ricinus communis; Role; Rosemary; Salvia miltiorrhiza; Source; Terpenes; Work; improved; innovation; insight; interest; isoprenoid; metabolic engineering; microbial disease; novel; pathogen; public health relevance; scaffold; tool

DESCRIPTION (provided by applicant): Natural products have a proven record of providing a significant fraction, either directly or as lead compounds, of human medicines. Among these, the terpenoids (isoprenoids) stand out as being the largest class (>50,000 already known), with the diterpenoids targeted here making up a significant fraction (>11,000 known). Indeed, the extensive diversification of diterpenoids indicates that these natural products provide a rich source of biological activity, with a number of these being used as pharmaceuticals (e.g., TaxolTM and the tanshinones) and/or research tools (e.g., phorbol esters). In addition, some LRDs serve important physiological roles in the native producing organisms - e.g., in plant defense against microbial diseases. Accordingly, we propose here to continue our productive investigation of the biosynthetic enzymes required to produce bioactive diterpenoids. Specifically, we will build on our previous work in this area, which includes elucidation of novel diterpenoid metabolic networks. This proposal then advances our long-term goal of engineering enzymes and metabolic pathways for the production of targeted libraries and specific individual terpenoid 'natural' products to benefit human health. In particular, the objective of this proposal is investigation of novel diterpenoid metabolism in a variety of plants, including the important crop plant rice as well as medicinal herbs. Accordingly, our studies have important implications for providing increased access to diterpenoid natural products, whose extensive diversification suggests that these are built upon privileged scaffolds from which biological activity is readily derived.

描述（由申请人提供）：天然产品具有直接或作为先导化合物提供人用药物的重要部分的证明记录。其中，萜类化合物（类异戊二烯）是最大的类别（已知> 50，000种），其中目标二萜类化合物占很大一部分（已知> 11，000种）。事实上，二萜类化合物的广泛多样化表明这些天然产物提供了丰富的生物活性来源，其中许多被用作药物（例如，紫杉醇TM和丹参酮）和/或研究工具（例如，佛波醇酯）。此外，一些LRD在天然生产生物体中发挥重要的生理作用-例如，在植物防御微生物疾病方面。因此，我们建议在这里继续我们的生产调查所需的生物合成酶产生生物活性的二萜类化合物。具体来说，我们将建立在我们以前的工作在这一领域，其中包括阐明新的二萜类代谢网络。然后，该提案推进了我们的长期目标，即工程化酶和代谢途径，用于生产靶向文库和特定的单个萜类化合物“天然”产品，以造福人类健康。特别是，这项建议的目的是 是对多种植物中新的二萜类化合物代谢的研究，包括重要的农作物水稻以及药用植物。因此，我们的研究具有重要的意义，提供更多的二萜类天然产物，其广泛的多样化表明，这些是建立在特权的支架，生物活性是很容易得到的。