Five novel and highly efficient endophytic fungi isolated from Huperzia serrata expressing huperzine A for the treatment
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BIOTECHNOLOGICAL PRODUCTS AND PROCESS ENGINEERING
Five novel and highly efficient endophytic fungi isolated from Huperzia serrata expressing huperzine A for the treatment of Alzheimer’s disease Han Wen-Xia 1 & Han Zhong-Wen 2 & Jia Min 3 & Zhang Han 4 & Li Wei-Ze 4 & Yang Li-Bin 4 & Liang Fei 4 & Han Lu 4 & Zhao Ning 4 & Li Xiao-Feng 1 Received: 1 June 2020 / Revised: 30 August 2020 / Accepted: 5 September 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract Huperzine A (Hup A) is an important drug for treating Alzheimer’s disease (AD) and mainly extracted from the Huperzia serrata (Thunb.) Trevis. (Lycopodiaceae) (HS). Nevertheless, the content of Hup A in HS is very low of 0.007% with growing circle of 8 to 10 years, and the chemical synthesis of Hup A still has some insurmountable limitations in the industrialized production. So, the available resources of Hup A for clinical treatment of AD are scarce. The purpose of this work was to construct a biosynthesis platform based on the endophytic fungi from HS. In this work, five endophytic fungi Mucor racemosus NSH-D, Mucor fragilis NSY-1, Fusarium verticillioides NSH-5, Fusarium oxysporum NSG-1, and Trichoderma harzianum NSW-V were firstly found and isolated from the Chinese folk medicine HS, which were identified according to their morphological characteristics and nuclear ribosomal DNA ITS sequences. The highest efficient fungus could effectively biosynthesize Hup A in a liquid culture of 319.8 ± 0.17 mg/L which were 112 times higher than that of other reported conventional endophytic fungi. Moreover, these fungi with higher hereditary stability could possess the initial expressing ability of Hup A after 40 generations, and the expressed Hup A from these biosynthesis systems has prior physicochemical properties, a better inhibition activity of acetylcholinesterase and a lower cytotoxicity compared with the listed active pharmaceutical ingredients (APIs) of Hup A. These results provide promising alternative resources for producing Hup A at an industrial scale by biosynthesis, and it may also shed light on millions of AD patients. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00253-020-10894-4) contains supplementary material, which is available to authorized users. * Li Wei-Ze [email protected]
Zhao Ning [email protected]
Han Wen-Xia [email protected] Han Zhong-Wen [email protected]
Li Xiao-Feng [email protected] 1
College of Medical Technology, Xi’an Medical University, Xi’an 710021, People’s Republic of China
2
Department of Oncology, Fushan Hospital of Traditional Chinese Medicine of Tumor, Shijiazhuang 050200, People’s Republic of China
3
Shaanxi Key Laboratory of Ischemic Cardiovascular Disease, Institute of Basic and Translational Medicine, Xi’an Medical University, Xi’an 710021, Shaanxi, People’s Republic of China
4
College of Pharmacy, Xi’an Medical University, Xinwang road 1, Weiyang Zone, Xi’an 710021, People’s Republic of China
Jia Min [email protected] Zhang Han 2062594580@
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