Efficient strategy for maintaining and enhancing the huperzine A production of Shiraia sp. Slf14 through inducer elicitation

• Published in: Journal of industrial microbiology & biotechnology 2014-07, Vol.41 (7), p.1175-1179
• Main Authors: Yan, Riming, Zhang, Zhibin, Wang, Ya, Yang, Huilin, Zeng, Qinggui, Zhu, Du
• Format: Article
• Language: English
• Subjects: Acetic acid; acetylcholinesterase; Alkaloids - biosynthesis; Alkaloids - isolation & purification; Alzheimer disease; Alzheimer Disease - drug therapy; Alzheimer's disease; Analysis; Ascomycota - drug effects; Ascomycota - metabolism; Biochemistry; Bioinformatics; Biological and medical sciences; Biomedical and Life Sciences; bioprocessing; Biotechnology; Cell culture; Cell Extracts - pharmacology; Chemicals; Endophytes; Endophytes - drug effects; Endophytes - metabolism; Extraction processes; Fermentation; Fermentation - drug effects; Fundamental and applied biological sciences. Psychology; Fungi; Genetic Engineering; Huperzia; Huperzia - chemistry; Huperzia - cytology; Inorganic Chemistry; Laboratories; Life Sciences; Lycopodium; lysine; Lysine - metabolism; Lysine - pharmacology; Metabolites; Microbial Viability - drug effects; Microbiology; Plant extracts; Secondary Metabolism; Secondary metabolites; Sesquiterpenes - isolation & purification; Short Communication; Studies; viability
• ISSN: 1367-5435; 1476-5535
• DOI: 10.1007/s10295-014-1461-0

Huperzine A (HupA), a naturally occurring lycopodium alkaloid, is a potent, highly specific and reversible inhibitor of acetylcholinesterase and is a potential treatment for Alzheimer’s disease. However, isolating HupA from Huperziaceae plants is inefficient; thus, extracting this compound from endophytic fungi may be more controllable and sustainable. However, the large-scale production of this chemical from endophytes is limited by the innate instability of endophytic fungi. In this study, we maintained the stability and viability of the HupA-producing endophytic fungus Shiraia sp. Slf14 and enhanced the HupA titers during fermentation by adding Huperzia serrata extracts (HSE), L-lysine, and acetic acid into the culture as inducers. Adding trace amounts of HupA clearly improved the HupA production of Shiraia sp. Slf14, reaching a maximum content of approximately 40 μg g⁻¹. Moreover, the addition of HSE and L-lysine promoted HupA production in the flask fermentation. The aforementioned bioprocessing strategy may be potentially applied to other endophytic fungal culture systems for the efficient production of plant secondary metabolites.