1.上海中医药大学创新中药研究院手性药物研究中心(上海 201203)
钟雪庆,女,硕士研究生,主要从事中药活性分子的生物合成研究工作
赵群飞,博士,副研究员;E-mail: qunfeizhao@shutcm.edu.cn
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钟雪庆,赵群飞.藤仓赤霉菌中蟾毒灵7β⁃羟化酶的发现与功能鉴定[J].上海中医药杂志,2023,57(9):19-26.
ZHONG Xueqing,ZHAO Qunfei.Identification and functional characterization of a bufalin 7β⁃hydroxylase from Fusarium fujikuroi[J].Shanghai Journal of Traditional Chinese Medicine,2023,57(9):19-26.
钟雪庆,赵群飞.藤仓赤霉菌中蟾毒灵7β⁃羟化酶的发现与功能鉴定[J].上海中医药杂志,2023,57(9):19-26. DOI: 10.16305/j.1007-1334.2023.2305049.
ZHONG Xueqing,ZHAO Qunfei.Identification and functional characterization of a bufalin 7β⁃hydroxylase from Fusarium fujikuroi[J].Shanghai Journal of Traditional Chinese Medicine,2023,57(9):19-26. DOI: 10.16305/j.1007-1334.2023.2305049.
目的,2,挖掘能催化蟾蜍内酯类化合物特异性羟化修饰的酶,以促进名贵中药材蟾酥功效组分的开发与应用。,方法,2,采用同源序列比对挖掘藤仓赤霉菌(,Fusarium fujikuroi,)中的甾体羟化酶,通过毕赤酵母异源表达、工程菌株细胞转化以及代谢产物的分离与鉴定,从而确定酶的功能。,结果,2,以蟾蜍内酯类化合物蟾毒它灵、蟾毒灵为底物,毕赤酵母重组菌株KM71H-,FF294,转化蟾毒它灵没有产生明显的产物,而转化蟾毒灵时产生了羟化产物7β-羟基蟾毒灵。,结论,2,从藤仓赤霉菌中发现能催化蟾毒灵发生7β-羟化修饰的甾体羟化酶FF294,是目前文献报道首个能催化蟾蜍内酯类化合物羟基化反应的酶。
Objective,2,To explore enzymes that catalyze specific hydroxylation modification of bufadienolides so as to promote the development and application of the efficacy components of the rare traditional Chinese medicine Chansu (Bufonis Venenum).,Methods,2,The steroid hydroxylase from ,Fusarium fujikuroi ,was discovered by sequence alignment, and its function was determined by heterologous expression in ,Pichia pastoris ,and isolation and identification of the metabolites transformed by the engineered strains.,Results,2,The activity of the strain KM71H-,FF294, was investigated by using bufalin and bufotaline as substrates. No product was produced when KM71H-,FF294, transformed bufotaline, but the hydroxylation product 7β-OH bufalin was produced when bufalin was transformed.,Conclusion,2,Steroid hydroxylase FF294 from ,Fusarium fujikuroi, could catalyze the conversion of bufalin into 7β-hydroxylated products, and this is the first report of an enzyme that catalyzes the hydroxylation of bufadienolides.
蟾酥蟾蜍内酯类化合物羟化酶结构修饰活性成分中药研究
Chansu (Bufonis Venenum)bufadienolidessteroid hydroxylasestructural modificationactive componenttraditional Chinese medicine research
国家药典委员会. 中华人民共和国药典(2020年版):一部 [M]. 北京:中国医药科技出版社,2020: 265.
左其艳,赵彦敏,李振麟,等. 中药蟾酥的研究概况[J]. 人参研究,2017, 29(3): 48-51.
WANSAPURA A N, LASKO V, XIE Z, et al. Marinobufagenin enhances cardiac contractility in mice with ouabain-sensitive alpha1 Na+-K+-ATPase[J]. Am J Physiol Heart Circ Physiol, 2009, 296(6): H1833-H1839.
张慧卿,殷子斐,盛佳钰,等. 蟾酥的临床应用与研究现状[J]. 临床军医杂志,2012, 40(2): 477-480.
LI D, QU X, HOU K, et al. PI3K/Akt is involved in bufalin-induced apoptosis in gastric cancer cells[J]. Anticancer Drugs, 2009, 20(1): 59-64.
何孙香,吴中伟,刘梅芬. 华蟾酥毒基通过调控circNFIX/miR-577通路抑制乳腺癌MDA-MB-231细胞的增殖、迁移和侵袭[J]. 中国免疫学杂志,2023, 39(4): 770-776.
梁正敏,何家康,彭健波,等. 蟾酥醇提取物的体外抗炎作用研究[J]. 湖北农业科学,2016, 55(11): 2843-2845, 2848.
杨琳,段鹏飞,王琼,等. 蟾酥脂溶性提取物的分离分析及其镇痛、抗肿瘤作用研究[J]. 氨基酸和生物资源,2007, 29(1): 64-67.
殷佩浩. 中药蟾酥的研究进展[J]. 上海医药,2015, 36(10): 3-6.
陈瀛澜,郝艳艳,郭夫江,等. 蟾酥化学成分及药理活性研究进展[J]. 中草药,2017, 48(12): 2579-2588.
孙志国,高国峰,周珩. 中药活性成分微生物转化技术研究进展[J]. 黑龙江科技信息,2013, 15(25): 75.
YE M, QU G, GUO H, et al. Novel cytotoxic bufadienolides derived from bufalin by microbial hydroxylation and their structure-activity relationships[J]. J Steroid Biochem Mol Biol, 2004, 91(1-2): 87-98.
YE M, HAN J, TU G, et al. Microbial hydroxylation of bufalin by Cunninghamella blakesleana and Mucor spinosus[J]. J Nat Prod, 2005, 68(4): 626-628.
MA X C, XIN X L, LIU K X, et al. Microbial transformation of cinobufagin by Syncephalastrum racemosum[J]. J Nat Prod, 2008, 71(7): 1268-1270.
ZHAN J, GUO H, NING L, et al. Efficient preparation of derivatives of resibufogenin using microbial catalytic technique[J]. Planta Med, 2006, 72(4): 346-350.
MOU L Y, XIN X L, CHEN L, et al. Biotransformation of resibufogenin by Actinomucor elegans[J]. J Asian Nat Prod Res, 2014, 16(6): 623-628.
ZHANG W, YE M, QU G Q, et al. Microbial hydroxylation of cinobufagin by Mucor spinosus[J]. J Asian Nat Prod Res, 2005, 7(3): 225-259.
XIN X L, ZHAN L B, LI F Y, et al. Microbial transformation of bufotalin by Alternaria alternata AS 3.4578[J]. J Asian Nat Prod Res, 2009, 11(1): 7-11.
GHASEMI S, MOHAJERI M, HABIBI Z. Biotransformation of testosterone and testosterone heptanoate by four filamentous fungi[J]. Steroids, 2014, 92: 7-12.
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