Abstract
Huperzine A (HupA) is a plant alkaloid that is of great interest as a therapeutic candidate for the treatment of Alzheimer's disease. However, the current production of HupA from plants in large quantity is unsustainable because the plant resource is scarce and the content of HupA in plants is extremely low. Surprisingly, this compound was recently found to be produced by various endophytic fungi, which are much more controllable than the plants due to simpler genetics and ease of manipulation. However, it might be due to the innate properties of endophytic symbiosis, that production of this chemical in large quantity from endophytes has not yet been put into practice. Endophytic Colletotrichum gloeosporioides ES026 was previously isolated from a HupA producing plant and the fungi also proved to produce HupA. In this study, various fermentation conditions were tried to optimize the production of HupA from C. gloeosporioides ES026. Optimization of these parameters resulted in a 25.58% increase in HupA yield. Potato extracts supplemented with glucose or sucrose but not maltose facilitated HupA producing from the fungi. A final concentration of 0.5–2% ethanol stimulated the growth of fungi while methanol with the same treatment slightly inhibited the growth. However, both methanol and ethanol greatly increased the HupA production with the highest yield of HupA (51.89% increment) coming from ethanol treatment. Further analysis showed that both ethanol and methanol were strong inducers of HupA production, while ethanol was partially used as a carbon source during fermentation. It was noticed that the color of that ethanol treated mycelia gradually became dark while methanol treated ones stayed grey during fermentation. The present study sheds light on the importance of optimizing the fermentation process, which, combined with effective inducers, maximizes production of chemicals of important economic interest from endophytic fungi.
Highlights
Huperzine A (HupA), a pharmaceutical Lycopodium alkaloid ((5R, 9R, 11E)5-amino-11-ethylidene-5, 6, 9, 10-tetrahydro-7-methyl-5, 9methano-cycloocteno[b] pyridine-2(1H)-one), was first isolated from the traditional Chinese medicine Qian Ceng Ta (the whole plant of Huperzia serrata (Thunb. ex Murray) Trev. (Lycopodiaceae)) by Chinese scientists (Figure 1) [1,2]
We looked into several factors that could possibly promote C. gloeosporioides ES026 to producing higher yield of HupA during the fermentation
One HupAproducing strain was identified as C. gloeosporioides ES026, which produces the chemical approximate 25.47 mg?g21CDW of mycelia when the fungi were cultured in 28uC for 6 days
Summary
HupA, a pharmaceutical Lycopodium alkaloid ((5R, 9R, 11E)5-amino-11-ethylidene-5, 6, 9, 10-tetrahydro-7-methyl-5, 9methano-cycloocteno[b] pyridine-2(1H)-one), was first isolated from the traditional Chinese medicine Qian Ceng Ta (the whole plant of Huperzia serrata (Thunb. ex Murray) Trev. (Lycopodiaceae)) by Chinese scientists (Figure 1) [1,2]. H. serrata belongs to a lower class of plants from Lycopodiopsida and it has a very limited distribution and an extremely long vegetative cycle. It takes at least 15 years from spore germination through the gametophyte stage to reach the mature sporophyte stage [7]. Tissue culture for this plant is rarely successful (our own experience and correspondence with colleagues). The HupA on the pharmaceutical market is still predominantly extracted from plants, which results in the rapid decline of H. serrata in China due to over-harvesting [9]
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