Developing platforms for the production of diterpenoids (TSB application reference 43970-304155)

开发二萜类化合物生产平台（TSB 申请参考号 43970-304155）

• 批准号: BB/M018210/1
• 负责人: Ian Graham
• 金额: $ 305.5万
• 依托单位: University of York
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2015
• 资助国家: 英国
• 起止时间: 2015 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FM018210%2F1
• 关键词: Developing; platforms; production; diterpenoids; TSB

Plants produce a wide range of diterpenoids, many of which are used commercially such as a paclitaxel, employed in the treatment of cancers, and steviol glyclosides which are used as zero-calorie natural sweeteners. Many other useful diterpenoids cannot yet be commercially exploited due to their limited availability and/or high production costs. Using synthetic biology it is now possible to engineer organisms such as yeast so that they are able to convert simple sugars to high-value chemicals. This project will develop yeast, algae and higher plant species as "chassis organisms" which can be used for the scalable production of diterpenoids. Our project will focus in particular on compounds which could be used in the treatment of cancers, or used in skin products such as sunscreens to protect skin against harmful UV light. These biological production systems will also be useful in producing many other diterpenoids that are found in nature.

植物产生各种各样的二萜，其中许多用于商业用途，例如用于治疗癌症的紫杉醇，以及用作零热量天然甜味剂的甜菊醇糖苷。许多其他有用的二萜类化合物由于供应有限和/或生产成本高，尚不能进行商业开发。利用合成生物学，现在有可能改造酵母等生物，使它们能够将单糖转化为高价值的化学物质。该项目将开发酵母、藻类和高等植物物种作为“底盘生物”，可用于大规模生产二萜。我们的项目将特别关注可用于治疗癌症的化合物，或用于皮肤产品（如防晒霜）的化合物，以保护皮肤免受有害紫外线的伤害。这些生物生产系统也将有助于生产自然界中发现的许多其他二萜类化合物。

项目成果

Untapped resources for medical research.

未开发的医学研究资源。

• DOI: 10.1126/science.abc8085
• 发表时间: 2020
• 期刊: Science (New York, N.Y.)
• 作者: Pérez-Escobar OA

A Cytochrome P450-Mediated Intramolecular Carbon-Carbon Ring Closure in the Biosynthesis of Multidrug-Resistance-Reversing Lathyrane Diterpenoids.

• DOI: 10.1002/cbic.201600316
• 发表时间: 2016-09-02
• 期刊: CHEMBIOCHEM
• 影响因子: 3.2
• 作者: King, Andrew J.;Brown, Geoffrey D.;Gilday, Alison D.;Forestier, Edith;Larson, Tony R.;Graham, Ian A.
• 通讯作者: Graham, Ian A.

Gene discovery and virus-induced gene silencing reveal branched pathways to major classes of bioactive diterpenoids in Euphorbia peplus.

• DOI: 10.1073/pnas.2203890119
• 发表时间: 2022-05-24
• 期刊: Proceedings of the National Academy of Sciences of the United States of America
• 影响因子: 11.1

Engineering Production of a Novel Diterpene Synthase Precursor in Nicotiana benthamiana.

• DOI: 10.3389/fpls.2021.757186
• 发表时间: 2021
• 期刊: Frontiers in plant science
• 影响因子: 5.6
• 作者: Forestier ECF;Brown GD;Harvey D;Larson TR;Graham IA
• 通讯作者: Graham IA