精神活性特殊代谢物生物合成的新领域

IF 8.3 2区 生物学 Q1 PLANT SCIENCES
Ginny Li, Peter J. Facchini
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引用次数: 0

摘要

最近,迷幻药法规的放宽促使人们对迷幻药治疗焦虑、抑郁、创伤后应激和药物滥用等各种精神疾病的潜力进行了广泛的临床研究。大多数临床试验都依赖于在自然界中发现的少量已知分子,如迷幻药,或早已为人所知的天然代谢物的合成类似物,包括麦角酰二乙胺(LSD)。阐明了几种迷幻化合物的生物合成途径,为利用合成生物学作为合成化学的补充,制备新型衍生物提供了机会,这些衍生物的药理特性可能优于已知药物。在此,我们回顾了植物、真菌和动物产生具有重要药用价值的致幻专一代谢物伊博格碱、麦司卡林、迷幻药、麦角酸和 N,N-二甲基色胺(DMT)的途径的代谢生物化学。我们还总结了在微生物中重组这些途径的情况,并对整合本地和非本地酶来制备新型衍生物发表了评论。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
New frontiers in the biosynthesis of psychoactive specialized metabolites

The recent relaxation of psychedelic drug regulations has prompted extensive clinical investigation into their potential use to treat diverse mental health conditions including anxiety, depression, post-traumatic stress, and substance-abuse disorders. Most clinical trials have relied on a small number of known molecules found in nature, such as psilocybin, or long-known synthetic analogs of natural metabolites, including lysergic acid diethylamide (LSD). Elucidation of biosynthetic pathways leading to several psychedelic compounds has established an opportunity to use synthetic biology as a complement to synthetic chemistry for the preparation of novel derivatives with potentially superior pharmacological properties compared with known drugs. Herein we review the metabolic biochemistry of pathways from plants, fungi and animals that yield the medicinally important hallucinogenic specialized metabolites ibogaine, mescaline, psilocybin, lysergic acid, and N,N-dimethyltryptamine (DMT). We also summarize the reconstitution of these pathways in microorganisms and comment on the integration of native and non-native enzymes to prepare novel derivatives.

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来源期刊
Current opinion in plant biology
Current opinion in plant biology 生物-植物科学
CiteScore
16.30
自引率
3.20%
发文量
131
审稿时长
6-12 weeks
期刊介绍: Current Opinion in Plant Biology builds on Elsevier's reputation for excellence in scientific publishing and long-standing commitment to communicating high quality reproducible research. It is part of the Current Opinion and Research (CO+RE) suite of journals. All CO+RE journals leverage the Current Opinion legacy - of editorial excellence, high-impact, and global reach - to ensure they are a widely read resource that is integral to scientists' workflow.
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