Efficient strategy for maintaining and enhancing the huperzine A production of Shiraia sp. Slf14 through inducer elicitation

Oxford University Press (OUP) - Tập 41 Số 7 - Trang 1175-1179 - 2014
Yan Ren1,2, Zhibin Zhang1, Ya Wang3, Huilin Yang1, Qinggui Zeng1, Du Zhu1,3
1grid.411862.8 0000000087329757 Key Laboratory of Protection and Utilization of Subtropic Plant Resources of Jiangxi Province Jiangxi Normal University 330022 Nanchang China
2grid.449868.f Key Laboratory for Research on Active Ingredients in Natural Medicine of Jiangxi Province Yichun University 336000 Yichun China
3grid.411864.e Jiangxi Science and Technology Normal University 330013 Nanchang China

Tóm tắt

Abstract Huperzine A (HupA), a naturally occurring lycopodium alkaloid, is a potent, highly specific and reversible inhibitor of acetylcholinesterase and is a potential treatment for Alzheimer’s disease. However, isolating HupA from Huperziaceae plants is inefficient; thus, extracting this compound from endophytic fungi may be more controllable and sustainable. However, the large-scale production of this chemical from endophytes is limited by the innate instability of endophytic fungi. In this study, we maintained the stability and viability of the HupA-producing endophytic fungus Shiraia sp. Slf14 and enhanced the HupA titers during fermentation by adding Huperzia serrata extracts (HSE), l-lysine, and acetic acid into the culture as inducers. Adding trace amounts of HupA clearly improved the HupA production of Shiraia sp. Slf14, reaching a maximum content of approximately 40 μg g−1. Moreover, the addition of HSE and l-lysine promoted HupA production in the flask fermentation. The aforementioned bioprocessing strategy may be potentially applied to other endophytic fungal culture systems for the efficient production of plant secondary metabolites.

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Tài liệu tham khảo

Castillo, 1970, Biosynthesis of lycopodine. Incorporation of Δ1-piperideine and of pelletierine, Can J Chem, 48, 2911, 10.1139/v70-489

Castillo, 1970, Biosynthesis of lycopodine from lysine and acetate. The pelletierine hypothesis, Can J Chem, 48, 1893, 10.1139/v70-312

Comins, 1995, Model studies toward the synthesis of the lycopodium alkaloid, phlegmarine, J Org Chem, 60, 711, 10.1021/jo00108a039

Hemscheidt, 1993, Biosynthesis of lycopodine: incorporation of acetate via an intermediate with C2v symmetry, J Am Chem Soc, 115, 3020, 10.1021/ja00060a078

Ju, 2009, Isolation and preliminary identification of the endophytic fungi which produce Huperzine A from four species in Huperziaceae and determination of Huperzine A by HPLC, Fudan Univ J Med Sci, 36, 445

Koshiba, 2009, Total synthesis of (−)-huperzine A, Org Lett, 11, 5354, 10.1021/ol9022408

Kumar, 2013, Isolation, purification and characterization of vinblastine and vincristine from endophytic fungus Fusarium oxysporum isolated from Catharanthus roseus, PLoS One, 8, e71805, 10.1371/journal.pone.0071805

Kusari, 2011, Survival-strategies of endophytic Fusarium solani against indigenous camptothecin biosynthesis, Fungal Ecol, 4, 219, 10.1016/j.funeco.2010.11.002

Li, 2007, Study on fermentation condition for production of huperzine A from endophytic fungus 2F09P03B of Huperzia serrata, Chin Med Biotechnol, 2, 254

Luo, 2010, Comparison of 454-ESTs from Huperzia serrata and Phlegmariurus carinatus reveals putative genes involved in lycopodium alkaloid biosynthesis and developmental regulation, BMC Plant Biol, 10, 209, 10.1186/1471-2229-10-209

Luo, 2010, Analysis of expressed sequence tags from the Huperzia serrata leaf for gene discovery in the areas of secondary metabolite biosynthesis and development regulation, Physiol Plantarum, 139, 1, 10.1111/j.1399-3054.2009.01339.x

Ma, 2004, The lycopodium alkaloids, Nat Prod Rep, 21, 752, 10.1039/b409720n

Ma, 2008, In vitro production of huperzine A, a promising drug candidate for Alzheimer’s disease, Phytochemistry, 69, 2022, 10.1016/j.phytochem.2008.04.017

Ma, 2007, Huperzine A from Huperzia species—an ethnopharmacolgical review, J Ethnopharmacol, 113, 15, 10.1016/j.jep.2007.05.030

Marshall, 1975, Biosynthesis of lycopodine. The question of the intermediacy of piperidine-2-acetic acid, Can J Chem, 53, 41, 10.1139/v75-005

Nyembo, 1978, Phlegmarine, a likely key intermediate in the biosynthesis of the Lycopodium alkaloids, Can J Chem, 56, 851, 10.1139/v78-142

Qian, 1989, A total synthesis of (±)-huperzine A, Tetrahedron Lett, 30, 2089, 10.1016/S0040-4039(01)93719-0

Rafii, 2011, A phase II trial of huperzine A in mild to moderate Alzheimer disease, Neurology, 76, 1389, 10.1212/WNL.0b013e318216eb7b

Stierle, 1993, Taxol and taxane production by Taxomyces andreanae, an endophytic fungus of Pacific yew, Science, 260, 214, 10.1126/science.8097061

Sudhakar, 2013, Do endophytic fungi possess pathway genes for plant secondary metabolites?, Curr Sci India, 104, 178

Szypuła, 2005, Somatic embryogenesis and in vitro culture of Huperzia selago shoots as a potential source of huperzine A, Plant Sci, 168, 1443, 10.1016/j.plantsci.2004.12.021

Wang, 2011, Isolation and characterization of endophytic huperzine A-producing fungi from Huperzia serrata, J Ind Microbiol Biot, 38, 1267, 10.1007/s10295-010-0905-4

Yang, 2003, Select of producing podophyllotoxin endophytic fungi from podophyllin plant, Nat Product Res Dev, 15, 419

Yi, 2011, Characterization of a mutant strain of a filamentous fungus Cladosporium phlei for the mass production of the secondary metabolite phleichrome, J Microbiol, 49, 680, 10.1007/s12275-011-1022-4

Zhang, 2011, Endophytic fungus Cladosporium cladosporioides LF70 from Huperzia serrata produces huperzine A, World J Microbiol Biotechnol, 27, 479, 10.1007/s11274-010-0476-6

Zhao, 2013, Ethanol and methanol can improve huperzine A production from endophytic Colletotrichum gloeosporioides ES026, PLoS One, 8, e61777, 10.1371/journal.pone.0061777

Zhu, 2010, A novel endophytic huperzine A-producing fungus, Shiraia sp. Slf14, isolated from Huperzia serrata, J Appl Microbiol, 109, 1469, 10.1111/j.1365-2672.2010.04777.x

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Oxford University Press (OUP)

Tập 41 Số 7

1175-1179

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