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Production and enhancement of the acetylcholinesterase inhibitor, huperzine A, from an endophytic Alternaria brassicae AGF041

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Abstract

Huperzine A (HupA) is a potent acetylcholinesterase (AChE) inhibitor of a great consideration as a prospective drug candidate for Alzheimer’s disease treatment. Production of HupA by endophytes offers an alternative challenge to reduce the massive plant harvest needed to meet the increasing demand of HupA. In the current study, some endophytic fungal and actinobacterial isolates from the Chinese herb, Huperzia serrata, underwent liquid fermentation, alkaloid extraction, and screening for AChE inhibition and HupA production. Among these isolates, Alternaria brassicae AGF041 strain was the only positive strain for HupA production with the maximum AChE inhibition of 75.5%. Chromatographic analyses verified the identity of the produced HupA. The HupA production was efficiently maximized up to 42.89 μg/g of dry mycelia, after optimization of thirteen process parameters using multifactorial statistical approaches, Plackett–Burman and central composite designs. The statistical optimization resulted in a 40.8% increase in HupA production. This is the first report to isolate endophytic actinobacteria with anti-AChE activity from H. serrata, and to identify an endophytic fungus A. brassicae as a new promising start strain for a higher HupA yield.

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Acknowledgments

The authors are greatly thankful to Dr. M Ayaad, Dr. El-Sayed R. El-Sayed and Dr. Hany Aglan, lecturers in the Egyptian Atomic Energy Authority (EAEA), for the plant sample, and assistance in the TLC and HPLC analysis, respectively. This work was supported in part by the Nuclear Research Center, Atomic Energy Authority, Egypt.

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Authors and Affiliations

  1. Plant Research Department, Nuclear Research Center, Atomic Energy Authority, Cairo, Egypt

    Amira G. Zaki, Ashraf S. Ahmed & Ola E. A. Al-Hagar

  2. Department of Microbiology, Faculty of Science, Ain Shams University, Cairo, Egypt

    Einas H. El-Shatoury

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  1. Amira G. Zaki
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  2. Einas H. El-Shatoury
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  3. Ashraf S. Ahmed
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  4. Ola E. A. Al-Hagar
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Correspondence to Amira G. Zaki.

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Zaki, A.G., El-Shatoury, E.H., Ahmed, A.S. et al. Production and enhancement of the acetylcholinesterase inhibitor, huperzine A, from an endophytic Alternaria brassicae AGF041. Appl Microbiol Biotechnol 103, 5867–5878 (2019). https://doi.org/10.1007/s00253-019-09897-7

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