基因导向发现和摩洛因的核糖体生物合成
Roland D Kersten1, Lisa S Mydy1, Timothy R Fallon2,3
1Department of Medicinal Chemistry, University of Michigan, Ann Arbor, Michigan 48109, United States.
Journal of the American Chemical Society
|April 19, 2022
概括
科学家发现植物使用核糖体合成和转化后修饰 (RiPP) 途径制造莫里丁. 这为开发植物性癌症疗法开辟了新的途径.
科学领域:
- 生物化学
- 植物科学
- 药物发现
背景情况:
- 摩洛是一种植物性,具有治疗癌症的潜力,但很难生产.
- 现有分离和合成方法的产量很低,限制了药物开发.
研究的目的:
- 探索生物合成作为摩洛类双环的替代生产途径.
- 确定负责植物中莫里丁生物合成的酶.
主要方法:
- 采矿植物转录组以识别莫里丁前体和循环酶.
- 描述一个日本的kerria moroidin cyclase的功能.
- 在转基因烟草植物中生产多种moroidins,包括celogentin C.
主要成果:
- 摩洛类通过BURP域循环合成并经过翻译修饰 (RiPPs).
- 一种来自日本鱼的新型moroidin cyclase被发现并进行了鉴定.
- 转基因烟草植物成功产生细胞毒素C,对肺腺癌细胞具有毒性.
结论:
- 生物合成为生产莫罗类提供了可行的替代方案.
- 植物转录组采矿对于发现新生物活性循环及其酶是有效的.
- 这项研究为通过生物合成开发基于moroidin的治疗方法铺平了道路.
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