Response surface methodology‐mediated improvement of the irradiated endophytic fungal strain, Alternaria brassicae AGF041 for Huperzine A‐hyperproduction

Huperzine A (HupA) is an anti‐Alzheimer’s therapeutic and a dietary supplement for memory boosting that is extracted mainly from Huperziacae plants. Endophytes represent the upcoming refuge to protect the plant resource from distinction but their HupA yield is still far from commercialization. In this context, UV and gamma radiation mutagenesis of the newly isolated HupA‐producing Alternaria brassicae AGF041 would be applied in this study for improving the endophytic HupA yield. Compared to non‐irradiated cultures, UV (30–40 min, exposure) and γ (0·5 KGy, dose) irradiated cultures, each separately, showed a significant higher HupA yield (17·2 and 30·3%, respectively). While, application of a statistically optimized compound irradiation (0·70 KGy of γ treatment and 42·49 min of UV exposure, sequentially) via Response Surface Methodology (RSM) resulted in 53·1% production increase. Moreover, a stable selected mutant strain CM003 underwent batch cultivation using a 6·6 l bioreactor for the first time and was successful for scaling up the HupA production to 261·6 µg l−1. Findings of this research are demonstrated to be valuable as the employed batch fermentation represents a successful starting step towards the promising endophytic HupA production at an industrial scale. Significance and Impact of the Study: This study demonstrates that a stable Alternaria brassicae mutant strain CM003 generated from a statistically optimized compound mutation can improve the production of the anti‐Alzheimer’s drug Huperzine A (HupA) under submerged batch cultivation through a 6·6 l bioreactor. This would offer a novel white biotechnology for more effective and safer production of HupA for a large industrial application.