Abstract

Huperzine A (HupA) is an effective inhibitor of acetylcholinesterase and has attracted great interest as a therapeutic candidate for Alzheimer’s disease. However, the use of HupA is limited by resource scarcity as well as by its low yields from Huperzia serrata, its primary plant source. Recent studies have shown that this compound is produced by various endophytic fungi, thereby providing a promising alternative source, as fungi are much more amenable than plants owing to their simpler genetics and the ease of manipulation. In this review, we summarize the progress in research on the methods to increase HupA production, including fermentation conditions, fungal elicitors, gene expression, and the activation of key enzymes. This review provides guidance for further studies on HupA-producing endophytic fungi aimed at efficient HupA synthesis and accumulation, and offers new approaches for studies on the regulation of high-value bioactive secondary metabolites.

摘要

石杉碱甲（HupA）是一种有效的乙酰胆碱酯酶抑制剂，作为阿尔茨海默氏病的候选治疗剂引起了极大的兴趣。但是，HupA的使用受到资源稀缺以及石杉柏的低产的限制，它的主要植物来源。最近的研究表明，该化合物是由多种内生真菌产生的，从而提供了一种有希望的替代来源，因为真菌由于其更简单的遗传学和易于操作而比植物更易接受。在这篇综述中，我们总结了增加HupA产量的方法的研究进展，包括发酵条件，真菌诱导子，基因表达和关键酶的激活。这篇综述为进一步研究生产HupA的内生真菌，旨在有效地合成和积累HupA提供了指导，并为调节高价值生物活性次生代谢产物提供了新的方法。