Elucidating the elaboration of plant diterpenoid natural products

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大量人类药物的已证明记录。在这些化合物中，萜类化合物(异戊二烯)是最大的类别(已知的50,000种)，这里针对的二萜类化合物占相当大的比例(&gt；11,000已知)。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，其中一些被用作药物(例如紫杉醇TM和丹参酮)和/或研究工具(例如佛波酯)。此外，一些LRD在本地生产的生物体中发挥着重要的生理作用--例如，在植物防御微生物疾病方面。因此，我们建议继续对产生生物活性二萜类化合物所需的生物合成酶进行生产性研究。具体地说，我们将在这一领域的先前工作的基础上再接再厉，其中包括阐明新的二萜代谢网络。这项提议随后推进了我们的长期目标，即设计酶和代谢途径，以生产靶向文库和特定的个人萜类“天然”产品，以造福于人类健康。特别是，这项提案的目标是 研究了新的二萜类化合物在多种植物中的代谢，包括重要的粮食作物水稻和草药。因此，我们的研究对于提供更多的二萜类天然产物具有重要意义，这些天然产物的广泛多样性表明，这些产品建立在很容易获得生物活性的特权支架上。

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.