Ethanol and methanol can improve huperzine A production from endophytic Colletotrichum gloeosporioides ES026.
Ethanol and methanol can improve huperzine A production from endophytic Colletotrichum gloeosporioides ES026.
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乙醇和甲醇可以提高内生胶孢炭疽菌 ES026 的石杉碱甲产量
DOI：
10.1371/journal.pone.0061777
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Hu X
中科院分区：
文献类型：
--
作者：
Zhao XM;Wang ZQ;Shu SH;Wang WJ;Xu HJ;Ahn YJ;Wang M;Hu X
石杉碱甲(HupA)是一种植物生物碱，是治疗阿尔茨海默病的候选药物。然而，由于植物资源稀缺，植物中HupA的含量极低，目前从植物中大量生产HupA是不可持续的。令人惊讶的是，最近发现这种化合物是由各种内生真菌产生的，由于更简单的遗传学和易于操作，这些真菌比植物更容易控制。然而，可能是由于内生共生的固有特性，内生真菌大量生产这种化学物质尚未投入实践。内生炭疽菌ES026是从一株产生HupA的植物中分离出来的，该真菌也被证明能产生HupA。本研究对胶孢霉ES026发酵产HupA的条件进行了优化。这些参数的优化使HupA的产率提高了25.58%。添加葡萄糖或蔗糖但不添加麦芽糖的马铃薯提取物促进了真菌产生HupA。最终浓度为0.5-2%的乙醇对真菌生长有促进作用，而相同处理的甲醇对真菌的生长有轻微的抑制作用。甲醇和乙醇均能显著提高HupA的产量，其中乙醇处理的HupA产量最高(增加51.89%)。进一步的分析表明，乙醇和甲醇都是HupA产生的强烈诱导剂，而乙醇在发酵过程中被部分用作碳源。在发酵过程中，乙醇处理的菌丝体颜色逐渐变暗，而甲醇处理的菌丝体颜色保持灰色。本研究揭示了优化发酵过程的重要性，发酵过程与有效的诱导剂相结合，最大限度地利用内生真菌生产具有重要经济价值的化学品。
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.
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