Research on endophytic fungi for producing huperzine A on a large-scale.

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.