基因鉴定和半合成的抗炎性oleanane类型的三基因wilforlide A A的基因鉴定和半合成
Yuan Liu1,2, Jiawei Zhou1,3, Panting Liu1
1School of Traditional Chinese Medicine, Capital Medical University, Beijing, 100069, China.
The New phytologist
|November 28, 2023
概括
研究人员确定了合成wilforlide A的关键基因,这是一种具有抗炎性质的化合物. 他们设计了酵母来生产wilforlide A,提供了一个独立于植物的生产方法.
科学领域:
- 自然产品生物合成 自然产品生物合成
- 代谢工程是代谢工程.
- 分子生物学分子生物学
背景情况:
- 威尔福利德A是Tripterygium wilfordii Hook F的关键活性化合物,具有显著的抗炎和免疫抑制作用.
- 威尔福利德A的生物合成途径,尽管结构简单,但以前没有被阐明.
- 了解威尔福利德A生物合成对于开发替代生产战略至关重要.
研究的目的:
- 鉴定和描述涉及威尔福利德A.生物合成的基因.
- 建立一种代谢工程方法,用于在异质宿主中产生wilforlide A.
- 通过途径复制使wilforlide A的半合成成为可能.
主要方法:
- 基因特异性表达分析和基因组挖掘以确定候选基因.
- 鉴定基因的体外和体外功能特征.
- 使用模块化两步 (M2S) 和CRISPR-Cas9技术构建工程酵母.
主要成果:
- 在wilforlide A生物合成中催化C-22氧化C-450 TwCYP82AS1细胞染色体的鉴定.
- 发现TwCYP712K1到K3酶氧化C-29氧化在烯和烯类型三烯中.
- 在工程酵母中成功复制生物合成途径,从而产生abrusgenic酸.
结论:
- 这项研究阐明了wilforlide A生物合成中的关键酶性步骤.
- 工程酵母成功生产了abrusgenic acid,这是wilforlide A半合成的前体.
- 这项工作提供了一个新的代谢工程策略,用于生产wilforlide A,独立于植物提取.
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