纤姿拟青霉YS-13发酵罐扩大培养产石杉碱甲的初步研究A Preliminary Study on the Production of Huperzine A Via Expanding Cultivation of Paecilonmyces tennis YS-13 in Fermenter
苏经迁;刘辉英;郭凯;庄依凡;杨民和;
摘要(Abstract):
在7.0 L自动生物发酵罐中开展纤姿拟青霉(Paecilonmyces tennis)菌株YS-13的放大培养试验,并研究了不同培养阶段的各项发酵参数的变化情况.结果表明:P.tennis YS-13在发酵罐扩大培养条件下石杉碱甲的产量达到20.0μg·mL(-1),其中待测组分B5-8对乙酰胆碱酯酶的半数抑制浓度(ρIC50)为2.38mg·mL(-1),其中待测组分B5-8对乙酰胆碱酯酶的半数抑制浓度(ρIC50)为2.38mg·mL(-1);同时获得了P.tennis YS-13在发酵罐培养过程中p H值、菌体质量浓度、产物浓度等参数的变化情况,为今后的工艺优化奠定了基础.
关键词(KeyWords): 自动生物发酵罐;石杉碱甲;纤姿拟青霉(Paecilonmyces tennis YS-13);扩大培养
基金项目(Foundation): 福建省科技厅重点项目(2012N0013);; 福建省中青年教师教育科研项目(JAT160107)
作者(Authors): 苏经迁;刘辉英;郭凯;庄依凡;杨民和;
参考文献(References):
- [1]FERREIRA A,RODRIHUES M,FORTUNA A,et al.Huperzine A from Huperzia serrata:a review of its sources,chemistry,pharmacology and toxicology[J].Phytochemistry Reviews,2016,15(1):1-35.
- [2]DAMAR U,GERSNER R,JOHNSTONE J T,et al.Huperzine A as a neuroprotective and antiepileptic drug:a review of preclinical research[J].Expert Rev Neurother,2016,16:671-680.
- [3]SZYPULAA W,PIETROSIUKA A,SUCHOCKIB P,et al.Somatic embryogenesis and in vitro culture of Huperzia selago shoots as a potential source of Huperzine A[J].Plant Science,2005,168:1443-1452.
- [4]BIENAIM C,MELIN A,BENSADDEK L,et al.Effects of plant growth regulators on cell growth and alkaloids production by cell cultures of Lycopodiella inundata[J].Plant Cell,Tissue and Organ Culture(PCTOC),2015,123(3):523-533.
- [5]MA X,GANG D R.In vitro production of Huperzine A,a promising drug candidate for Alzheimer's disease[J].Phytochemistry,2008,69:2022-2028.
- [6]WANG M,SUN M,HAO H,et al.Avertoxins A-D,Prenyl asteltoxin derivatives from aspergillus versicolor Y10,an endophytic fungus of Huperzia serrata[J].Journal of Natural Products,2015,78(12):3067-3070.
- [7]XIONG Z Q,YANG Y Y,LIU Q X,et al.Endophytes in the plant Huperzia serrata:fungal diversity and discovery of a new pentapeptide[J].Archives of Microbiology,2015,197(3):411-418.
- [8]WANG Y,ZENG Q,ZHANG Z,et al.Isolation of endophytic fungi from Huperzia serrata and their acetylcholinesterase inhibitory activity[J].China Journal of Chinese Materia Medica,2011,36:734-740.
- [9]黎万奎,周吉燕,林子为,等.蛇足石杉内生真菌2F09P03B产石杉碱甲发酵条件的研究[J].中国医药生物技术,2007,2:254-259.
- [10]汪涯,颜日明,曾庆桂,等.一株产石杉碱甲的蛇足石杉内生真菌的分离和鉴定[J].菌物学报,2011,30:255-262.
- [11]JU Z,WANG J,LI P S.Isolation and preliminary identification of the endophytic fungi which produce Huperzine A from four species in Huperziaceae and determination of Huperzine A by HPLC[J].Fudan Univ J Med Sci,2009,36:445-449.
- [12]ZHANG Z B,ZENG Q G,YAN R M,et al.Endophytic fungus Cladosporium cladosporioides LF70 from Huperzia serrata produces Huperzine A[J].World J Microb Biot,2011,27:479-486.
- [13]SU J Q,YANG M H.Huperzine A production by Paecilomyces tenuis YS-13,an endophytic fungus isolated from Huperzia serrata[J].Natural Product Research,2015,29:1035-1041.
- [14]苏经迁,黄彬,邱慧,等.产生物碱和石杉碱甲蛇足石杉内生真菌的初步研究[J].中国药学杂志,2011,46:1477-1481.
- [15]ZHU D,WANG J,ZENG Q,et al.A novel endophytic Huperzine A-producing fungus,Shiraia sp.Slf14,isolated from Huperzia serrata[J].Journal of Applied Microbiology,2010,109:1469-1478.
- [16]ZHAO X M,WANG Z Q,SHU S H,et al.Ethanol and Methanol can improve huperzine A production from endophytic Colletotrichum gloeosporioides ES026[J].Plos One,2013,8(4):392-392.
- [17]杨晓军,高霞,任树林,等.一株Streptosporangium sp.的次生代谢产物的研究[J].天然产物研究与开发,2006,18:366-368.
- [18]DONG L H,FAN S W,LING Q Z,et al.Indentification of Huperzine A-producing endophytic fungi isolated from Huperzia serrata[J].World J Microbiol Biotechnol,2013,30(3):1011-1017.
- [19]STIERLE A,STROBEL G,STIERLE D,et al.The search for a taxol-producing microorganism among the endophytic fungi of the pacific yew,Taxus brevifolia[J].J Nat Prod,1995,58:13-15.
- [120]LI J Y,SIDHU R S,BOLLON A,et al.Stimulation of taxol production in liquid cultures of Pestalotiopsis microspore[J].Mycol Res,1998,102:461-464.
- [21]YANG H,PENG S,ZHANG Z,et al.Molecular cloning,expression,and functional analysis of the copper amine oxidase gene in the endophytic fungus Shiraia sp.Slf14 from Huperzia serrata[J].Protein Expression and Purification,2016,128:8-13.
- [22]YAN R,ZHANG Z,WANG Y,et al.Efficient strategy for maintaining and enhancing the Huperzine A production of Shiraia sp.Slf14 through inducer elicitation[J].J Ind Microbiol Biotechnol,2014,41:1175-1179.
- [23]YANG H,WANG Y,ZHANG Z,et al.Whole-genome shotgun assembly and analysis of the genome of Shiraia sp.strain Slf14,a novel endophytic fungus producing Huperzine A and Hypocrellin A[J].Genome announcements,2013,2(1):343-349.
- [24]ZELIK P,LUKESOVA A,VOLOSHKO L N,et al.Screening for acetylcholinesterase inhibitory activity in cyanobacteria of the genus Nostoc[J].Journal of Enzyme Inhibition and Medicinal Chemistry,2009,24:531-536.
- [25]WILLIAMSON S M,MOFFAT C,GOMERSALL M A,et al.Exposure to acetylcholinesterase inhibitors alters the physiology and motor function of honeybees[J].Frontiers in Physiology,2013,4:13.
- [26]WANG C,WU J,MEI X.Enhancement of Taxol production and excretion in Taxus chinensis cell culture by fungal elicitation and medium renewal[J].Appl Microbiol Biotechnol,2001,55(4):404-410.