加兰他敏和石杉碱甲生物合成的研究进展

Advances in biosynthesis of galanthamine and huperzine A

植物来源的加兰他敏、石杉碱甲等乙酰胆碱酯酶抑制剂(AChEIs)以其高效低毒的优势成为当前临床治疗阿尔茨海默病的主流药物。由于目前加兰他敏、石杉碱甲等AChEIs尚未实现工业规模化合成,故仍主要依赖植物提取。然而,药源植物培育周期长、难度大,药效物质含量低,随着社会需求的急剧攀升,供求矛盾日益突出。开发新替代资源以及利用现代基因工程技术合成加兰他敏、石杉碱甲等AChEIs是缓解当前矛盾的有效途径。对近年来加兰他敏和石杉碱甲生物合成的相关研究进展进行综述,总结了替代资源的开发研究现状,以期为挖掘加兰他敏、石杉碱甲等AChEIs优势新资源及利用代谢工程合成药效物质研究提供参考。

Acetylcholinesterase inhibitors(AChEIs) isolated from plants have become the mainstream of clinical treatment for Alzheimer’s disease because of their high efficiency and low toxicity. At present, the production of galantamine and huperzine A still mainly rely on plant extraction since they are not chemically synthesized on a large scale in industry. However, with the sharp rise of social demand, the contradiction between supply and demand has become increasingly prominent due to the difficulty in cultivation and the poor abundance of effective substances. Developing new alternative resources and taking the advantage of metabolic engineering for the production of AChEIs such as galantamine and huperzine are the efficient ways to alleviate the current contradiction. Here, the current development status of alternative resources was summarized and the progress of biosynthesis of galantamine and huperzine A during the past few years was reviewed.