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

Abstract

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.

Unlocking the biosynthetic potential of Penicillium roqueforti for hyperproduction of the immunosuppressant mycophenolic acid: Gamma radiation mutagenesis and response surface optimization of fermentation medium

“…In the literature, improvement of MPA-producing strains by random mutation was reported as improvement of P. brevicompactum using UV 21 , and P. roqueforti spore suspension using both UV and gamma rays. [11][12][13] Additionally, application of gamma irradiation proved its efficiency for enhancing many essential fungal metabolites such as the antitumor drug taxol from Epicoccum nigrum 22 , A. fumigatus, and A. tenuissima 23 , the anti-Alzheimer's candidate huperzine A from Alternaria brassicae 24 , and the cardiac glycoside digoxin from Epicoccum nigrum 25 . Moreover, gamma irradiation could improve the heavy metal tolerance of fungi 26 .…”

Novel fabrication of SiO2/Ag nanocomposite by gamma irradiated Fusarium oxysporum to combat Ralstonia solanacearum

“…From literature, a gamma irradiation dose of 1000 Gy was applied to Monascus purpureus resulting in improving the biosynthesis yield of selenium NPs under SSF (El-Sayed et al 2020b ) as well as enhancing the biosynthesis of cobalt-ferrite nanoparticles using cell free filtrates from irradiated culture under submerged fermentation (El-Sayed et al 2020a ). Previous studies proved that the gamma irradiation at appropriate dosages can improve the production of a variety of fungal metabolites (El-Sayed et al 2020c ; Zaki et al 2021 ).…”

Biosorption optimization of lead(II) and cadmium(II) ions by two novel nanosilica-immobilized fungal mutants

“…Response surface methodology, including central composite and Box–Behnken, is a statistical modelling tool for estimating the behaviour of process parameters and understanding their interactions on the investigated response (process output) (El‐Sayed & Zaki, 2022; Saeed et al, 2020, 2021; Zaki et al, 2019, 2021, 2022; Zaki & El‐Sayed, 2021) Thus, RSM is an efficient methodology for improving and optimizing bioprocesses. In literature, Ahmady‐Asbchin (2016) proved the efficiency of the Box–Behnken model of RSM using Design‐Expert software to optimize Cd +2 biosorption on Pseudomonas aeruginosa with a maximum capacity of 0.56 mmol g −1 .…”

“…Gamma irradiation is a successful approach to physical mutations. It has been widely applied in producing industrially useful metabolites by endophytic microbial mutants (El‐Sayed et al, 2020; Zaki et al, 2020, 2021). Conversely, Gamma irradiation has rarely been used in microbial modification to enhance their HM biosorption (Wang & Sun, 2013).…”