Li Wei, Wang Zhicheng, Zhu Qiuyu, Tian Pingfang
Beijing Key Laboratory of Bioprocess, College of Life Science and Technology, Beijing University of Chemical Technology, Beijing 100029, China.
Molecules. 2025 Jun 23;30(13):2704. doi: 10.3390/molecules30132704.
Huperzine A (HupA) can alleviate Alzheimer's disease due to its reversible inhibition of acetylcholinesterase (AChE). The chemical synthesis and plant extraction of HupA is plagued by route complexity and resource scarcity, respectively. Although some endophytic fungi from can independently biosynthesize HupA, their yields are trivial. After a comprehensive investigation of HupA-producing across China, we focused on the endophytic fungi from Hunan and Hubei provinces, which demonstrated high-level HupA. Morphological characteristics and internal transcriptional sequence (ITS) analysis revealed their diversity. Among the four HupA-producing endophytic fungi, is the best-performing and was thus subjected to fermentation optimization. When its fermentation medium was supplemented with flavonoids daidzein and apigenin, HupA yields reached 58.38 μg/g (dry cell weight, dcw) and 72.21 μg/g dcw, respectively. In contrast, the addition of L-lysine and extracts led to yields of 50.17 μg/g dcw and 255.32 μg/g dcw, respectively. Transcriptomic analysis revealed that extracts substantially upregulated the expression of HupA biosynthesis genes in . Overall, extracts outperformed L-lysine, daidzein, and apigenin in boosting HupA production, as they encompass all the necessary nutrients for growth. This study not only connotes a nutritional exchange between and during long-term coevolution but also offers insights for harnessing plant extracts for the overproduction of desired metabolites in endophytic fungi.
石杉碱甲（HupA）可通过可逆性抑制乙酰胆碱酯酶（AChE）来缓解阿尔茨海默病。HupA的化学合成和植物提取分别存在路线复杂和资源稀缺的问题。尽管一些内生真菌能够独立生物合成HupA，但其产量很低。在对中国各地产HupA的内生真菌进行全面调查后，我们聚焦于来自湖南和湖北的内生真菌，它们表现出较高水平的HupA。形态学特征和内部转录间隔区（ITS）分析揭示了它们的多样性。在四种产HupA的内生真菌中，[具体真菌名称]表现最佳，因此对其进行了发酵优化。当在其发酵培养基中添加黄酮类化合物大豆苷元和芹菜素时，HupA产量分别达到58.38 μg/g（干细胞重量，dcw）和72.21 μg/g dcw。相比之下，添加L-赖氨酸和[具体提取物名称]提取物后，产量分别为50.17 μg/g dcw和255.32 μg/g dcw。转录组分析表明，[具体提取物名称]提取物显著上调了[具体真菌名称]中HupA生物合成基因的表达。总体而言，[具体提取物名称]提取物在提高HupA产量方面优于L-赖氨酸、大豆苷元和芹菜素，因为它们包含了[具体真菌名称]生长所需的所有营养物质。这项研究不仅暗示了[具体真菌名称]与[具体植物名称]在长期共同进化过程中的营养交换，还为利用植物提取物促进内生真菌中所需代谢产物的过量生产提供了见解。
