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Investigating (di)terpenoid biosynthesis

研究（二）萜类生物合成

基本信息

批准号：
10651726
负责人：
REUBEN JOHN PETERS
金额：
$ 53.72万
依托单位：
IOWA STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-06-01 至 2024-11-30
项目状态：
已结题

项目摘要

Natural products have a proven record of providing a significant fraction, either directly or as lead compounds, of human medicines. Among natural products, the terpenoids (isoprenoids) stand out as being the largest class (>50,000 already known), with the 20-carbon diterpenoids targeted here forming a significant fraction of these (>12,000 known). The extensive diversification of diterpenoids indicates that the manifold hydrocarbon skeletons that can be formed from this C20 backbone, particularly the decalin core ring structure found in the labdane-related diterpenoids (>7,000 known), provide privileged scaffolds for derivation of biological activity. Indeed, a number of these labdane-related diterpenoids are used as pharmaceuticals (e.g., the antibiotic mutilins) or are being investigated for such use (e.g., the tanshinones, triptolide, andrographolide, etc.). In addition, we have contributed to the discovery that the human pathogen Mycobacterium tuberculosis utilizes labdane-related diterpenoid metabolism in construction of an immune-modulatory factor. Accordingly, we propose here to continue our productive studies of the biosynthetic enzymes required to produce bioactive diterpenoids. Specifically, we will build on our previous work in this area, which includes investigations of enzymatic structure-function that have provided novel biosynthetic access to an array of diterpenoids, as well as elucidation of strategically selected diterpenoid metabolic networks. This MIRA proposal covers our systematic studies in this area, advancing our long-term goal of engineering enzymes and metabolic pathways for the production of targeted libraries and specific individual terpenoid ‘natural’ products, which are being already using for investigation of pharmaceutical utility.

天然产品已被证明可以直接或以铅的形式提供相当大的一部分

项目成果

期刊论文数量（19）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Tanshinones: Leading the way into Lamiaceae labdane-related diterpenoid biosynthesis.

DOI：
10.1016/j.pbi.2022.102189
发表时间：
2022-04
期刊：
Current opinion in plant biology
影响因子：
9.5
作者：
Wang Z;Peters RJ
通讯作者：
Peters RJ

Doing the gene shuffle to close synteny: dynamic assembly of biosynthetic gene clusters.

进行基因洗牌以关闭同步：生物合成基因簇的动态组装。

DOI：
10.1111/nph.16631
发表时间：
2020-08
期刊：
The New phytologist
影响因子：
0
作者：
Peters RJ
通讯作者：
Peters RJ

Expansion within the CYP71D subfamily drives the heterocyclization of tanshinones synthesis in Salvia miltiorrhiza.

DOI：
10.1038/s41467-021-20959-1
发表时间：
2021-01-29
期刊：
Nature communications
影响因子：
16.6
作者：
Ma Y;Cui G;Chen T;Ma X;Wang R;Jin B;Yang J;Kang L;Tang J;Lai C;Wang Y;Zhao Y;Shen Y;Zeng W;Peters RJ;Qi X;Guo J;Huang L
通讯作者：
Huang L

Dissecting the labdane-related diterpenoid biosynthetic gene clusters in rice reveals directional cross-cluster phytotoxicity.