克拉阿片类药物的生物合成
Kyunghee Kim1, Mohammadamin Shahsavarani2, Jorge Jonathan Oswaldo Garza-García2
1Department of Biological Sciences, Brock University, St. Catharines, ON, L2S 3A1, Canada.
The New phytologist
|July 31, 2023
概括
研究人员阐明了米特拉基宁生物合成途径,使微生物产生卡拉类阿片类药物. 这一突破为传统阿片类药物提供了潜在的替代品,具有更安全的副作用.
科学领域:
- 生物化学 生物化学
- 药理学 药理学是指药理学的学科.
- 植物科学 植物科学
背景情况:
- 米特拉吉宁 (Mitragynine) 是一种来自Mitragyna speciosa (kratom) 的类化合物,由于其有利的副作用概况,它是临床阿片类药物的潜在止痛替代品.
- 尽管东南亚传统上用于疼痛和刺激,但米特拉基宁的生物合成途径仍然没有特征.
- 了解这种途径对于探索Kratom的治疗潜力和开发新型止痛药至关重要.
研究的目的:
- 为了识别和表征参与米特拉基因生物合成途径的基因.
- 为了实现微生物生物合成的mitragynine及其立体同位素,speciogynine.
- 通过酶乱交来探索产生克拉阿片类衍生物的潜力.
主要方法:
- 搜索了克拉和Rubiaceae家族的转录组,寻找生物合成基因.
- 对已识别的酶进行了体外和体外功能研究.
- 利用来自各种来源的酶,包括Psilocybe cubensis和Hamelia patens,以重建酵母和大肠杆菌中的途径.
- 作为微生物生物合成的前体,供应了胺和secologanin.
主要成果:
- 在SABATH家族中确定了几种减少酶和一种新型的醇甲基转移酶.
- 从Hamelia patens发现了一种甲基转移酶,催化了该途径的最后一步.
- 通过使用异种酶和微生物宿主,成功实现了米特拉基宁和特异基宁的四步微生物生物合成.
- 证明了酶乱交,表明了模拟合成的潜力.
结论:
- 已经阐明了米特拉基宁生物合成途径,完成了我们对其形成的理解.
- 克拉阿片类药物的微生物生物合成首次实现,为可持续生产开辟了道路.
- 已识别的酶和途径为开发新型克拉衍生止痛药和探索其治疗应用提供了基础.
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