通过酵母代谢工程,阐明了阿什瓦甘达中基因组的基因集群,这些基因集群是阿什瓦甘达中 withanolide生物合成的基础
Erin E Reynolds1,2,3,4, Marena Trauger1,3, Fu-Shuang Li1,3,4
1Institute for Plant-Human Interface, Northeastern University, Boston, MA, USA.
Nature plants
|January 30, 2026
概括
研究人员阐明了阿什瓦甘达 (Withania somnifera) 中的withanolide生物合成途径,确定了生产这些医学上重要的化合物的关键基因. 这一发现使得用于制药应用的可持续生物制造成为可能.
科学领域:
- 植物分子生物学 植物分子生物学
- 代谢工程是代谢工程.
- 自然产品生物合成 自然产品生物合成
背景情况:
- 维他诺化物,来自Withania somnifera (阿什瓦甘达) 的类固醇乳,具有显著的神经,抗癌和适应性特性.
- 维他诺化物大部分未知的生物合成途径限制了它们的制药应用和大规模生产.
研究的目的:
- 为了阐明W. somnifera.中的维他诺化物生物合成途径.
- 为了识别关键的基因和酶参与withanolide生产.
- 为了使维他诺利德的可持续生物制造.
主要方法:
- 产生了W. somnifera的染色体规模的基因组组合.
- 鉴定了涉及与hanolide生物合成的特定组织基因集群.
- 在酵母中利用了代谢工程,在Nicotiana benthamiana中使用异质表达,在W. somnifera中使用病毒诱导的基因沉默.
主要成果:
- 阐明了通往一个关键的中介物与hanolide的途径.
- 鉴定了乳环形成的CYP87G1,CYP749B2和SDH2.
- 发现CYP88C7,CYP88C10和SULF1用于A环结构生成,其中SULF1发挥着核心途径作用.
结论:
- 这项研究揭示了维他诺化生物合成中的关键酶,包括硫转移酶 (SULF1) 的新型核心功能.
- 这项工作为工程生物合成和维他诺利德的可持续生产铺平了道路.
- 这些发现支持基于withanolide支架的新疗法开发.
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