周迪;潘齐冬;晏秀祥;高路;杨立新;
ZHOU Di;PAN Qi-dong;YAN Xiu-xiang;GAO Lu;YANG Li-xin;School of Ethnic Medicine, Yunnan Minzu University;Kunming Institute of Botany, Chinese Academy of Sciences;

• 1:云南民族大学民族医药学院
• 2:中国科学院昆明植物研究所

摘要(Abstract)：

甾体皂苷类化学成分是滇重楼中数量和含量最多的一类重要天然有机化合物，具有较好的生物活性。以甾体皂苷类化学成分为底物，利用微生物转化来获取大量结构新颖、活性优良的甾体皂苷，能为甾体药物的研发提供功能性的先导化合物。该文系统综述了滇重楼中甾体皂苷类化学成分及相关化学成分微生物转化研究进展，发现滇重楼中共有甾体皂苷类化学成分112个，其中，有8个甾体皂苷被作为底物，通过25种微生物参与了35个转化反应，转化率最高可达95%,使用频率最高的底物是薯蓣皂苷元，并对转化反应中使用的菌株、培养基、反应条件、转化率以及转化反应特征变化和转化产物的生物活性进行了归纳总结，以期为深入研究滇重楼甾体皂苷类化学成分的微生物转化提供参考。
Steroidal saponins, important natural organic compounds in Paris polyphylla var. yunnanensis, have good biological activity. Structural modification of steroidal saponins by microbial transformation could produce a large number of products with novel structures and excellent bioactivity, which can provide functional compounds for the research and development of steroidal drugs. This study summarized the research progress in steroidal saponins and their microbial transformation in P. polyphylla var. yunnanensis. P. polyphylla var. yunnanensis contains 112 steroidal saponins, 8 of which are used as substrates in 35 transformation reactions by 25 microbial species, with the highest transformation rate of 95%. Diosgenin is the most frequently used substrate. Furthermore, the strains, culture medium, reaction conditions, transformation rate, transformation reaction characteristics, and biological activities of the transformed products were summarized. This review may provide reference for the further research on microbial transformation of steroidal saponins in P. polyphylla var. yunnanensis.

关键词(KeyWords)： 滇重楼;甾体皂苷;微生物转化;真菌和细菌;进展
Paris polyphylla var.yunnanensis;steroidal saponins;microbial transformation;fungi and bacteria;progress

Abstract:

Keywords:

基金项目(Foundation): 国家自然科学基金面上项目(31970357)

作者(Authors): 周迪;潘齐冬;晏秀祥;高路;杨立新;
ZHOU Di;PAN Qi-dong;YAN Xiu-xiang;GAO Lu;YANG Li-xin;School of Ethnic Medicine, Yunnan Minzu University;Kunming Institute of Botany, Chinese Academy of Sciences;

DOI: 10.19540/j.cnki.cjcmm.20220506.204

参考文献(References)：

• [1] 刘玉雨，徐福荣，范敏，等.重楼属植物在少数民族医药中的应用[J].世界科学技术(中医药现代化),2019,21(3):449.
• [2] 王跃虎，牛红梅，张兆云，等.重楼属植物的药用价值及其化学物质基础[J].中国中药杂志，2015,40(5):833.
• [3] 杨远贵，张霁，张金渝，等.重楼属植物化学成分及药理活性研究进展[J].中草药，2016,47(18):3301.
• [4] 孟巍，杜娟，陈涛.重楼的化学成分及其抗肿瘤机制[J].生命的化学，2020,40(1):70.
• [5] 肖肖.薯蓣皂苷及其苷元的微生物转化研究[D].北京：中国科学院研究生院，2011.
• [6] 李慧杰.新月弯孢霉CICC40301转化3-酮-4-烯甾体化合物的研究[D].天津：天津科技大学，2018.
• [7] 刘靖.微生物转化甾体药物关键中间体4AD的研究[D].福州：福州大学，2004.
• [8] 苏海林.甾体衍生物羟基化的生物转化研究进展[J].化工管理，2020,575(32):41.
• [9] 罗卓玛，胡越高，王璐红，等.薯蓣皂苷元抗肿瘤衍生物的合成及其生物活性的研究[J].有机化学，2018,38(4):919.
• [10] 高冉冉，郜昭慧，董欣然，等.淡紫青霉ACCC31890对纤细薯蓣皂苷的生物转化[J].中国药师，2017,20(6):988.
• [11] 管鑫，李若诗，段宝忠，等.重楼属植物化学成分、药理作用研究进展及质量标志物预测分析[J].中草药，2019,50(19):4838.
• [12] 黄伟光，周俊.重楼的甾体皂素配基成分研究[J].云南医学杂志，1962,4(1):64.
• [13] NOHARA T,YABUTA H,SUENOBU M,et al.Steroid glycosides in Paris polyphylla Sm.[J].Chem Pharm Bull,2008,21(6):1240.
• [14] 陈昌祥，周俊.滇产植物皂素成分的研究Ⅴ.滇重楼的甾体皂甙和β-蜕皮激素[J].云南植物研究，1981,3(1):89.
• [15] QIN X J,SUN D J,NI W,et al.Steroidal saponins with antimicrobial activity from stems and leaves of Paris polyphylla var.yunnanensis [J].Steroids,2012,77(12):1242.
• [16] WANG Y,GAO W Y,LIU X Q,et al.Anti-tumor constituents from Paris polyphylla [J].Asian J Tradit Med,2005,1(1):7.
• [17] WU X,WANG L,WANG G C,et al.New steroidal saponins and sterol glycosides from Paris polyphylla var.yunnanensis [J].Planta Med,2012,78(15):1667.
• [18] 陈昌祥，周俊.五指莲重楼的甾体皂甙(2)[J].云南植物研究，1987,9(2):239.
• [19] SINGH B S,THAKUR R S,SCHULTEN H R.Spirostanol saponins from Paris polyphylla,structures of polyphyllin C,D,E and F [J].Phytochemistry,1982,21(12):2925.
• [20] WU X,WANG L,WANG H,et al.Steroidal saponins from Paris polyphylla var.yunnanensis [J].Phytochemistry,2012,81(3):133.
• [21] WEI J C,GAO W Y,YAN X D,et al.Chemical constituents of plants from the genus Paris [J].Cheminform,2015,45(50):1277.
• [22] 康利平，马百平，张洁，等.重楼中甾体皂苷的分离与结构鉴定[J].中国药物化学杂志，2005,15(1):32.
• [23] ZHAO Y,KANG L P,LIU Y X,et al.steroidal saponins from the rhizome of Paris polyphylla and their cytotoxic activities [J].Planta Med,2009,75(4):356.
• [24] MIYAMURA M,NAKANO K,NOHARA T.Steroid saponins from Paris polyphylla Sm.-supplement [J].Chem Pharm Bull,1982,30(2):712.
• [25] 陈昌祥，连红兵，李运昌，等.滇重楼种子中的甾体皂甙[J].云南植物研究，1990,12(4):452.
• [26] 陈昌祥.滇重楼地上部分的两个微量皂甙[J].云南植物研究，1995,17(2):111.
• [27] 陶俊杰，杨杰，闻晓东.滇重楼地上部分化学成分研究[J].中国药科大学学报，2020,51(4):454.
• [28] 黄伟光.滇产植物的皂素成分研究Ⅲ.重楼属植物的皂甙及皂甙元[J].药学学报，1965,12(10):657.
• [29] 陈昌祥，周俊.滇重楼的两个新甾体皂甙元[J].云南植物研究，1992,14(1):111.
• [30] 陈昌祥，周俊，张玉童，等.滇重楼地上部分的甾体皂甙[J].云南植物研究，1990,12(3):323.
• [31] MATSUDA H,PONGPIRUYADACHA Y,MORIKAWA T,et al.Protective effects of steroid saponins from Paris polyphylla var.yunnanensis on ethanol-or indomethacin induced gastric mucosal lesions in rats:structural requirement for activity and mode of action [J].Bioorg Med Chem Lett,2003,13(6):1101.
• [32] QIN X J,YU M Y,NI W,et al.Steroidal saponins from stems and leaves of Paris polyphylla var.yunnanensis [J].Phytochemi-stry,2016,121(10):20.
• [33] 蒋维，李小辉，万近福，等.云南重楼地上部分小极性化学成分研究[J].中药材，2021,44(1):84.
• [34] 徐暾海，毛晓霞，徐雅娟，等.云南重楼中的新甾体皂苷[J].高等学校化学学报，2007,28(12):2303.
• [35] ZHAO Y,KANG L P,LIU Y X,et al.Three new steroidal saponins from the rhizome of Paris polyphylla [J].Magn Reson Chem,2007,45(9):739.
• [36] KANG L P,LIU Y X,EICHHORN T,et al.Polyhydroxylated steroidal glycosides from Paris polyphylla [J].J Nat Prod,2012,75(6):1201.
• [37] 陈昌祥，张玉童，周俊.滇重楼地上部分的配糖体[J].云南植物研究，1995,17(4):473.
• [38] WEN Y S,NI W,QIN X J,et al.Steroidal saponins with cytotoxic activity from the rhizomes of Paris polyphylla var.yunnanensis [J].Phytochem Lett,2015,12:31.
• [39] 赵子璇，李春峰，杨洪旺，等.五环三萜类化合物微生物转化研究进展[J].天然产物研究与开发，2021,33(8):1415.
• [40] FENG B,MA B P,KANG L P,et al.The microbiological transformation of steroidal saponins by Curvularia lunata [J].Tetrahedron Lett,2005,61(49):11758.
• [41] 刘翊.中药重楼皂苷的分离、结构鉴定及生物转化的研究[D].天津：天津科技大学，2009.
• [42] 杜晨晖，张剑，余伯阳.Gliocladium deliquescens NRRL 1086对偏诺皂苷元的生物转化研究[J].天然产物研究与开发，2013,25(8):1017.
• [43] SHOHEL H,YOSHIO S.Microbiological transformation of diosgenin [J].J Org Chem,1963,28(10):2742.
• [44] LI L Q,ZHAO Y Q,LANG B Y,et al.Microbial transformation of diosgenin of diosgenone by Wickerhamomyces anomalus JQ-1 obtained from Naxi traditional Jiu Qu [J].Bioorg Chem,2020,95:103508.
• [45] 吴广畏.两株真菌转化薯蓣皂苷元的研究[D].杨凌：西北农林科技大学，2010.
• [46] DONG T,WU G W,WANG X N,et al.Microbiological transformation of diosgenin by resting cells of filamentous fungus,Cunninghamella echinulata CGMCC 3.2716 [J].J Mol Catal B Enzym,2010,67(3/4):251.
• [47] WU G W,GAO J M,SHI X W,et al.Microbial transformations of diosgenin by the white-rot basidiomycete Coriolus versicolor [J].J Nat Prod,2011,74:2095.
• [48] ZHAO Y,SUN L M,WANG X N,et al.Microbial transformation of diosgenin by Syncephalastrum racemosum (Cohn) Schroe-ter [J].Chin Chem Lett,2010,21(1):76.
• [49] ZHAO Y,SUN L M,WANG X N,et al.Hydroxylation of diosgenin by Absidia coerulea [J].Nat Prod Commun,2010,5(3):373.
• [50] ADHAM N Z,ZAKI R A,NAIM A.Microbial transformation of diosgenin and its precursor furostanol glycosides [J].World J Microbiol Biotechnol,2009,25(3):481.
• [51] KANEKO K,MITSUHASHI H,HIRAYAMA K.Microbial transformation of steroid.I.Microbiological hydroxylation of diosgenin [J].Chem Pharm Bull,1969,17(10):2031.
• [52] XIAO X,LIU X K,FU S B,et al.Microbial transformation of diosgenin by filamentous fungus Cunninghamella echinulata [J].J Asian Nat Prod Res,2011,13(3):270.
• [53] BLUNDEN G,PATEL A V,CRABB T A.Microbiological transformations of hecogenin and diosgenin by Cunninghamella elegans [J].Phytochemistry,1990,29(6):1771.
• [54] 王婧怡.杂色云芝生物转化薯蓣皂苷元的研究[D].杨凌：西北农林科技大学，2011.
• [55] MIN X,XIAO K H,XIANG G T,et al.Microbial transformation of diosgenin by Cunninghamella blakesleana AS 3.970 and potential inhibitory effects on P-glycoprotein of its metabolites [J].RSC Adv,2015,5 (95):78081.
• [56] 田茵.人参、薯蓣皂苷元的微生物转化及抗肿瘤活性研究[D].北京：北京大学，2004.
• [57] 关松磊，吴雅馨，孙赫，等.微生物转化技术在中药开发中的应用进展[J].微生物学通报，2018,45(4):900.
• [58] SANUNDERS R,CHEETHAM P S J,HARDMAN R.Microbial transformation of crude fenugreek steroids [J].Enzyme Microb Technol,1986,8(9):549.
• [59] WANG F Q,ZHANG C G,LI B,et al.New microbiological transformations of steroids by Streptomyces virginiae IBL-14 [J].Environ Sci Technol,2009,43(15):5967.
• [60] WANG F Q,LI B,WANG W,et al.Biotransformation of diosgenin to nuatigenin-type steroid by a newly isolated strain,Streptomyces virginiae IBL-14 [J].Appl Microbiol Biotechnol,2007,77(4):771.
• [61] 魏娟.云南重楼内生菌的分离鉴定及其对重楼皂甙的生物转化研究[D].无锡：江南大学，2014.
• [62] HE D X,LI G H,GU X T,et al.A new agent developed by biotransformation of polyphyllin Ⅶ inhibits chemoresistance in breast cancer [J].Oncotarget,2015,7(22):31814.
• [63] WANG Y H,SHI M,NIU H M,et al.Substituting one Paris for another in vitro cytotoxic and in vivo antitumor activities of Paris forrestii,a substitute of Paris polyphylla var.yunnanensis [J].J Ethnopharmacol,2018,218:45.
• [64] 陈雪莲，陶欣艺，王玮，等.薯蓣皂苷元及其维吉尼链霉菌IBL-14转化产物体外抑制人乳腺癌细胞Bcap37的作用研究[J].华东理工大学学报(自然科学版),2010,36(3):360.