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人类药物的先导化合物提供重要部分的证明记录。其中，萜类化合物（类异戊二烯）是最大的一类（已知的bb1,000），而这里所针对的二萜类化合物占很大一部分（已知的bb1,000）。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在本地生产生物中起着重要的生理作用-例如，在植物防御微生物疾病中。因此，我们建议在此继续对生产生物活性二萜所需的生物合成酶进行生产性研究。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代谢网络。该提案推进了我们的长期目标，即工程酶和代谢途径，以生产目标文库和特定的个体萜类“天然”产品，以造福人类健康。特别是这一建议的目标

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.