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

Abstract

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.

Role of Plant Derived Alkaloids and Their Mechanism in Neurodegenerative Disorders

“…Different strategies have been done to develop the alternative sources of huperzine A because it occurs in slow growing members of Huperziaceae . This includes Phlegmariurus aquarrosus in vitro tissue culture 183 and extraction from endophytic fungi which is secluded from huperzine A manufacturing herb 184 , 185 .…”

Plant alkaloids as drug leads for Alzheimer's disease

“…Therefore, there is strong interest in developing alternative sources of huperzine A. Attempted strategies include in vitro tissue culture of Phlegmariurus squarrosus, a member of Huperziaceae that produces higher concentrations of huperzine A (Ma and Gang, 2008); extraction of huperzine A from endophytic fungi isolated from huperzine A-producing herbs (Su and Yang, 2014;Yan et al, 2014); and the total synthesis of naturally occurring stereoisomer (−)huperzine A from commercially abundant (R)-pulegone (Ding et al, 2012).…”

Research Advances and Detection Methodologies for Microbe-Derived Acetylcholinesterase Inhibitors: A Systemic Review

“…Slf14 being the best producer (327.8 μg/L of the fermentation product) [ 44 ]. The optimal culturing conditions and molecular properties have been set for this strain [ 27 , 44 , 64 , 65 , 66 ].…”