萝芙木属植物药理活性和单萜吲哚生物碱合成途径研究进展
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摘要
萝芙木属植物中的蛇根木是印度传统草药,目前萝芙木属植物成为中国常用南药,主要用于治疗高血压、精神类疾病、心血管疾病、癌症等。对国产萝芙木属植物资源种类及分布、药理活性、萝芙木单萜吲哚生物碱的合成途径等研究进展进行综述,为萝芙木属植物的研究和临床应用提供参考。
Rauvolfia serpentine is a traditional Indian medicine and now the genus Rauvolfia becomes a commonly used south medicine in China. Rauvolfia is mainly used to treat hypertension, mental illness, cardiovascular disorders, cancer, and other diseases. The paper overviewed the main species and distribution, pharmacological properties, and the monoterpenoid indole alkaloids biosynthetic pathway of Rauvolfia in China. The paper aims to provide reference for research and clinical application in plants of the genus Rauvolfia.
Rauvolfia serpentine is a traditional Indian medicine and now the genus Rauvolfia becomes a commonly used south medicine in China. Rauvolfia is mainly used to treat hypertension, mental illness, cardiovascular disorders, cancer, and other diseases. The paper overviewed the main species and distribution, pharmacological properties, and the monoterpenoid indole alkaloids biosynthetic pathway of Rauvolfia in China. The paper aims to provide reference for research and clinical application in plants of the genus Rauvolfia.
引文
[1]Singh M,Kaur R,Rajput R,et al.Evaluating the therapeutic efficiency and drug targeting ability of alkaloids present in Rauwolfia serpentina[J].Int J Green Pharm,2017,11(3):132-142.
[2]Jerie P.Milestones of cardiovascular therapy.IV.Reserpine[J].Casopís Lékar Ceskych,2007,146(7):573-577.
[3]曹福祥,徐庆军,王承南,等.萝芙木属植物的物种和分布[J].中南林业科技大学学报,2007,27(6):154-158.
[4]冯毓秀,王云萍,楼之岑.国产萝芙藤的降压作用[J].药学学报,1981,16(1):45-52.
[5]林茂,于德泉,刘欣,等.红果萝芙木季胺碱的化学研究[J].药学学报,1985,20(2):198-202.
[6]张丽珍,杨冬业,袁盼盼.红果萝芙木植物组织培养及快速繁殖[J].江苏农业科学,2015,43(6):44-46.
[7]戴斌,丘翠嫦.广西产六种萝芙木的资源调查及鉴定[J].中国民族民间医药,2003,61(2):114-116.
[8]Biradar N,Hazarika I,Chandy V.Current insight to the uses of Rauwolfia:A review[J].Res Rev:J Pharmacogn,2016,3(3):1-4.
[9]Bunkar A R.Phytochemical and antimicrobial study of Rauwolfia serpentina[J].Int J Biol Res,2017,2(2):13-16.
[10]Chauhan S,Kaur A,Pareek R K.Pharmacobotanical and pharmacological evaluation of ayurvedic crude drug:Rauwolfia serpentina(Apocynaceae)[J].Int J Green Pharm,2018,11(4):S686-S693.
[11]Gicquel T,Hugbart C,Le Devehat F,et al.Death related to consumption of Rauvolfia sp.powder mislabeled as Tabernanthe iboga[J].Forensic Sci Int,2016,doi:10.1016/j.forsciint.2016.06.014.
[12]Keshavan M S.The tale of Rauwolfia Serpentina and the contributions of Asian Psychiatry[J].Asian J Psychiatr,2011,4(3):214-215.
[13]Nammi S,Boini K M,Koppula S,et al.Reserpineinduced central effects:Pharmacological evidence for the lack of central effects of reserpine methiodide[J].Can JPhysiol Pharmacol,2005,83(6):509-515.
[14]Pathania S,Ramakrishnan S M,Randhawa V,et al.SerpentinaDB:A database of plant-derived molecules of Rauvolfia serpentina[J].BMC Complement Altern Med,2015,doi:10.1186/s12906-015-0683-7.
[15]Ezeigbo I I,Ezeja M I,Madubuike K G,et al.Antidiarrhoeal activity of leaf methanolic extract of Rauwolfia serpentina[J].Asian Pac J Trop Biomed,2012,2(6):430-432.
[16]Abdelfatah S A,Efferth T.Cytotoxicity of the indole alkaloid reserpine from Rauwolfia serpentina against drug-resistant tumor cells[J].Phytomedicine,2015,22(2):308-318.
[17]Bemis D L,Capodice J L,Gorroochurn P,et al.Anti-prostate cancer activity of a beta-carboline alkaloid enriched extract from Rauwolfia vomitoria[J].Int JOncol,2006,29(5):1065-1073.
[18]Bhadane B S,Patil M P,Maheshwari V L,et al.Ethnopharmacology,phytochemistry,and biotechnological advances of family Apocynaceae:A review[J].Phytother Res,2018(2):1-30.
[19]Sabde S,Bodiwala H S,Karmase A,et al.Anti-HIVactivity of Indian medicinal plants[J].J Nat Med Tokyo,2011,65(3/4):662-669.
[20]Bisong S A,Brown R,Osim E E.Comparative effects of Rauwolfia vomitoria and chlorpromazine on locomotor behaviour and anxiety in mice[J].J Ethnopharmacol,2010,132(1):334-339.
[21]Elisabetsky E,Costacampos L.The alkaloid alstonine:Areview of its pharmacological properties[J].Evid-Based Compl Alt Med,2006,3(1):39-48.
[22]Bisong S A,Abuo F E,Udefa A L,et al.Comparative effects of alkaloid and saponin fractions of Rauwolfia vomitoria on social behaviour and depression in a CD1mouse model of memory impairment[J].Arch Curr Res Int,2019,16(1):1-11.
[23]Amoateng P,Quansah E,Karikari T K,et al.Medicinal plants used in the treatment of mental and neurological disorders in Ghana[J].Evid-Based Compl Alt Med,2018,doi:10.1155/2018/8590381.
[24]Ajao A A,Alimi A A,Olatunji O A,et al.A synopsis of anti-psychotic medicinal plants in Nigeria[J].Trans RSoc S Afr,2018,73(1):33-41.
[25]Tekwu E M,Bosompem K M,Anyan W K,et al.In vitro aassessment of anthelmintic activities of Rauwolfia vomitoria(Apocynaceae)stem bark and roots against parasitic stages of Schistosoma mansoni and cytotoxic study[J].J Parasitol Res,doi:10.1155/2017/2583969.
[26]Attah S K,Ayeh-Kumi P F,Sittie A A,et al.Extracts of Euphorbia hirta Linn.(Euphorbiaceae)and Rauvolfia vomitoria Afzel(Apocynaceae)demonstrate activities against Onchocerca volvulus microfilariae in vitro[J].BMCCompl Alter Med,2013,doi:10.1186/1472-6882-13-66.
[27]Pathania S,Randhawa V,Bagler G.Prospecting for novel plant-derived molecules of Rauvolfia serpentina as inhibitors of Aldose Reductase,a potent drug target for diabetes and its complications[J].PLo S One,2013,8(4):e61327.
[28]Campbell-Tofte J I,Molgaard P,Josefsen K,et al.Randomized and double-blinded pilot clinical study of the safety and anti-diabetic efficacy of the Rauvolfia-Citrus tea,as used in Nigerian traditional medicine[J].JEthnopharmacol,2011,133(2):402-411.
[29]Azmi M B,Qureshi S A,Ahmed S D H,et al.Ameliorative effect of hydro-methanolic extract from roots of Rauwolfia serpentina on some biochemical parameters of type 1 diabetic mice[J].Pak J Pharm Sci,2018,31(Suppl 2):663-668.
[30]Yu J,Chen Q.Antitumor activities of Rauwolfia vomitoria extract and potentiation of gemcitabine effects against pancreatic cancer[J].Integr Cancer Ther,2014,13(3):217-225.
[31]Dong R,Chen P,Chen Q.Inhibition of pancreatic cancer stem cells by Rauwolfia vomitoria extract[J].Oncol Rep,2018,40(6):3144-3154.
[32]Salehi B,Kumar N V A,Sener B,et al.Medicinal plants used in the treatment of human immunodeficiency virus[J].Int J Mol Sci,2018,doi:10.3390/ijms19051459.
[33]Chauhan S,Kaur A,Vyas M,et al.Comparison of antidiabetic and antioxidant activity of wild and cultivated variety of Rauwolfia serpentina[J].Asian JPharm Clin Res,2017,10(12):404-406.
[34]Afsheen N,Khalil U R,Jahan N,et al.Cardioprotective and metabolomic profiling of selected medicinal plants against oxidative stress[J].Oxid Med Cell Longev,2018,doi:10.1155/2018/9819360.
[35]Zaitseva O O,PoleZhaeva T V,Khudvakov A N,et al.Application of pectin rrom Rauvolfia serpentina(L.)Benth to the cryopreservation of human leucocyte cell suspensions[J].Cryo Lett,2018,39(1):72-78.
[36]Khudyakov A N,Kuleshova L G,Zaitseva O O,et al.Effect of pectins on water crystallization pattern and integrity of cells during freezing[J].Biopreserv Biobank,2019,17(1):52-57.
[37]Bakhtiarpoor M M,Setorki M P,Kaffashian M R P.Effects of essential oil of Satureja bachtiarica Bunge in a rat model of reserpine-induced depression[J].Iran J Med Sci,2018,43(4):409-415.
[38]Peres F F,Levin R,Suiama M A,et al.Cannabidiol prevents motor and cognitive impairments induced by reserpine in rats[J].Front Pharmacol,2016,doi:10.3389/fphar.2016.00343.
[39]Bispo J M M,Melo J E C,Gois A M,et al.Sex differences in the progressive model of parkinsonism induced by reserpine in rats[J].Behav Brain Res,2019,doi:10.1016/j.bbr.2019.01.041.
[40]Leal P C,Bispo J M M,Engelberth R C G J,et al.Serotonergic dysfunction in a model of parkinsonism induced by reserpine[J].J Chem Neuroanat,2019,doi:10.1016/j.jchemneu.2018.12.011.
[41]Isyraqiah F,Kutty K,Durairajanayagam D,et al.Effect of reserpine on the expression of tumour promoter,tumour suppressor and ulcer healing genes in the stomach of female Sprague-Dawley rats[J].Int Med J,2019,26(1):2-6.
[42]Mossoba M E,Flynn T J,Vohra S,et al.Human kidney proximal tubule cells are vulnerable to the effects of Rauwolfia serpentina[J].Cell Biol Toxicol,2016,31(6):285-293.
[43]Barleben L,Panjikar S,Ruppert M,et al.Molecular architecture of strictosidine glucosidase:The gateway to the biosynthesis of the monoterpenoid indole alkaloid family[J].Plant Cell,2007,19(9):2886-2897.
[44]Ma X,Panjikar S,Koepke J,et al.The structure of Rauvolfia serpentina strictosidine synthase is a novel six-bladed beta-propeller fold in plant proteins[J].Plant Cell,2006,18(4):907-920.
[45]Stoeckigt J,Panjikar S.Structural biology in plant natural product biosynthesis--architecture of enzymes from monoterpenoid indole and tropane alkaloid biosynthesis[J].Nat Prod Rep,2007,24(6):1382-1400.
[46]Xia L,Ruppert M,Wang M,et al.Structures of alkaloid biosynthetic glucosidases decode substrate specificity[J].ACS Chem Biol,2012,7(1):226-234.
[47]St?ckigt J,Panjikar S,Ruppert M,et al.The molecular architecture of major enzymes from ajmaline biosynthetic pathway[J].Phytochem Rev,2007,6(1):15-34.
[48]Bayer A,Ma X,St?ckigt J.Acetyltransfer in natural product biosynthesis--functional cloning and molecular analysis of vinorine synthase[J].Bioorgan Med Chem,2004,12(10):2787-2795.
[49]Sun L,Chen Y,Rajendran C,et al.Crystal structure of perakine reductase,founding member of a novel aldo-keto reductase(AKR)subfamily that undergoes unique conformational changes during NADPH binding[J].J Biol Chem,2012,287(14):11213-11221.
[50]Sun L,Ruppert M,Sheludko Y,et al.Purification,cloning,functional expression and characterization of perakine reductase:The first example from the AKRenzyme family,extending the alkaloidal network of the plant Rauvolfia[J].Plant Mol Biol,2008,67(5):455-467.
[51]Dang T T,Franke J,Tatsis E C,et al.Dual catalytic activity of a cytochrome P450 controls bifurcation at a metabolic branch point of alkaloid biosynthesis in Rauwolfia serpentina[J].Angew Chem Int Ed Engl,2017,56(32):9440-9444.
[52]Pasquali G,Porto D D,Fettneto A G.Metabolic engineering of cell cultures versus whole plant complexity in production of bioactive monoterpene indole alkaloids:Recent progress related to old dilemma[J].JBiosci Bioeng,2006,101(4):287-296.
[53]Kutchan T M,Hampp N,Lottspeich F,et al.The cDNAclone for strictosidine synthase from Rauvolfia serpentina.DNA sequence determination and expression in Escherichia coli[J].Febs Lett,1988,237(7):40-44.
[54]Gantet P,Memelink J.Transcription factors:Tools to engineer the production of pharmacologically active plant metabolites[J].Trends Pharmacol Sci,2002,23(12):563-569.
[55]Pauw B,Hilliou F A O,Martin V S,et al.Zinc finger proteins act as transcriptional repressors of alkaloid biosynthesis genes in Catharanthus roseus[J].J Biol Chem,2004,279(51):52940-52948.
[56]Prakash P,Rajakani R,Gupta V.Transcriptome-wide identification of Rauvolfia serpentina micro RNAs and prediction of their potential targets[J].Comput Biol Chem,2016,doi:10.1016/j.compbiolchem.2015.12.002.
[57]Góngora-Castillo E,Childs K L,Fedewa G,et al.Development of transcriptomic resources for interrogating the biosynthesis of monoterpene indole alkaloids in medicinal plant species[J].PLo S One,2012,7(12):e52506.
[58]Corbin C,Lafontaine F,Sepúlveda L J,et al.Virus-induced gene silencing in Rauwolfia species[J].Protoplasma,2017,254(4):1813-1818.
[59]Kellner F,Kim J,Clavijo B J,et al.Genome-guided investigation of plant natural product biosynthesis[J].Plant J,2015,82(4):680-692.
[2]Jerie P.Milestones of cardiovascular therapy.IV.Reserpine[J].Casopís Lékar Ceskych,2007,146(7):573-577.
[3]曹福祥,徐庆军,王承南,等.萝芙木属植物的物种和分布[J].中南林业科技大学学报,2007,27(6):154-158.
[4]冯毓秀,王云萍,楼之岑.国产萝芙藤的降压作用[J].药学学报,1981,16(1):45-52.
[5]林茂,于德泉,刘欣,等.红果萝芙木季胺碱的化学研究[J].药学学报,1985,20(2):198-202.
[6]张丽珍,杨冬业,袁盼盼.红果萝芙木植物组织培养及快速繁殖[J].江苏农业科学,2015,43(6):44-46.
[7]戴斌,丘翠嫦.广西产六种萝芙木的资源调查及鉴定[J].中国民族民间医药,2003,61(2):114-116.
[8]Biradar N,Hazarika I,Chandy V.Current insight to the uses of Rauwolfia:A review[J].Res Rev:J Pharmacogn,2016,3(3):1-4.
[9]Bunkar A R.Phytochemical and antimicrobial study of Rauwolfia serpentina[J].Int J Biol Res,2017,2(2):13-16.
[10]Chauhan S,Kaur A,Pareek R K.Pharmacobotanical and pharmacological evaluation of ayurvedic crude drug:Rauwolfia serpentina(Apocynaceae)[J].Int J Green Pharm,2018,11(4):S686-S693.
[11]Gicquel T,Hugbart C,Le Devehat F,et al.Death related to consumption of Rauvolfia sp.powder mislabeled as Tabernanthe iboga[J].Forensic Sci Int,2016,doi:10.1016/j.forsciint.2016.06.014.
[12]Keshavan M S.The tale of Rauwolfia Serpentina and the contributions of Asian Psychiatry[J].Asian J Psychiatr,2011,4(3):214-215.
[13]Nammi S,Boini K M,Koppula S,et al.Reserpineinduced central effects:Pharmacological evidence for the lack of central effects of reserpine methiodide[J].Can JPhysiol Pharmacol,2005,83(6):509-515.
[14]Pathania S,Ramakrishnan S M,Randhawa V,et al.SerpentinaDB:A database of plant-derived molecules of Rauvolfia serpentina[J].BMC Complement Altern Med,2015,doi:10.1186/s12906-015-0683-7.
[15]Ezeigbo I I,Ezeja M I,Madubuike K G,et al.Antidiarrhoeal activity of leaf methanolic extract of Rauwolfia serpentina[J].Asian Pac J Trop Biomed,2012,2(6):430-432.
[16]Abdelfatah S A,Efferth T.Cytotoxicity of the indole alkaloid reserpine from Rauwolfia serpentina against drug-resistant tumor cells[J].Phytomedicine,2015,22(2):308-318.
[17]Bemis D L,Capodice J L,Gorroochurn P,et al.Anti-prostate cancer activity of a beta-carboline alkaloid enriched extract from Rauwolfia vomitoria[J].Int JOncol,2006,29(5):1065-1073.
[18]Bhadane B S,Patil M P,Maheshwari V L,et al.Ethnopharmacology,phytochemistry,and biotechnological advances of family Apocynaceae:A review[J].Phytother Res,2018(2):1-30.
[19]Sabde S,Bodiwala H S,Karmase A,et al.Anti-HIVactivity of Indian medicinal plants[J].J Nat Med Tokyo,2011,65(3/4):662-669.
[20]Bisong S A,Brown R,Osim E E.Comparative effects of Rauwolfia vomitoria and chlorpromazine on locomotor behaviour and anxiety in mice[J].J Ethnopharmacol,2010,132(1):334-339.
[21]Elisabetsky E,Costacampos L.The alkaloid alstonine:Areview of its pharmacological properties[J].Evid-Based Compl Alt Med,2006,3(1):39-48.
[22]Bisong S A,Abuo F E,Udefa A L,et al.Comparative effects of alkaloid and saponin fractions of Rauwolfia vomitoria on social behaviour and depression in a CD1mouse model of memory impairment[J].Arch Curr Res Int,2019,16(1):1-11.
[23]Amoateng P,Quansah E,Karikari T K,et al.Medicinal plants used in the treatment of mental and neurological disorders in Ghana[J].Evid-Based Compl Alt Med,2018,doi:10.1155/2018/8590381.
[24]Ajao A A,Alimi A A,Olatunji O A,et al.A synopsis of anti-psychotic medicinal plants in Nigeria[J].Trans RSoc S Afr,2018,73(1):33-41.
[25]Tekwu E M,Bosompem K M,Anyan W K,et al.In vitro aassessment of anthelmintic activities of Rauwolfia vomitoria(Apocynaceae)stem bark and roots against parasitic stages of Schistosoma mansoni and cytotoxic study[J].J Parasitol Res,doi:10.1155/2017/2583969.
[26]Attah S K,Ayeh-Kumi P F,Sittie A A,et al.Extracts of Euphorbia hirta Linn.(Euphorbiaceae)and Rauvolfia vomitoria Afzel(Apocynaceae)demonstrate activities against Onchocerca volvulus microfilariae in vitro[J].BMCCompl Alter Med,2013,doi:10.1186/1472-6882-13-66.
[27]Pathania S,Randhawa V,Bagler G.Prospecting for novel plant-derived molecules of Rauvolfia serpentina as inhibitors of Aldose Reductase,a potent drug target for diabetes and its complications[J].PLo S One,2013,8(4):e61327.
[28]Campbell-Tofte J I,Molgaard P,Josefsen K,et al.Randomized and double-blinded pilot clinical study of the safety and anti-diabetic efficacy of the Rauvolfia-Citrus tea,as used in Nigerian traditional medicine[J].JEthnopharmacol,2011,133(2):402-411.
[29]Azmi M B,Qureshi S A,Ahmed S D H,et al.Ameliorative effect of hydro-methanolic extract from roots of Rauwolfia serpentina on some biochemical parameters of type 1 diabetic mice[J].Pak J Pharm Sci,2018,31(Suppl 2):663-668.
[30]Yu J,Chen Q.Antitumor activities of Rauwolfia vomitoria extract and potentiation of gemcitabine effects against pancreatic cancer[J].Integr Cancer Ther,2014,13(3):217-225.
[31]Dong R,Chen P,Chen Q.Inhibition of pancreatic cancer stem cells by Rauwolfia vomitoria extract[J].Oncol Rep,2018,40(6):3144-3154.
[32]Salehi B,Kumar N V A,Sener B,et al.Medicinal plants used in the treatment of human immunodeficiency virus[J].Int J Mol Sci,2018,doi:10.3390/ijms19051459.
[33]Chauhan S,Kaur A,Vyas M,et al.Comparison of antidiabetic and antioxidant activity of wild and cultivated variety of Rauwolfia serpentina[J].Asian JPharm Clin Res,2017,10(12):404-406.
[34]Afsheen N,Khalil U R,Jahan N,et al.Cardioprotective and metabolomic profiling of selected medicinal plants against oxidative stress[J].Oxid Med Cell Longev,2018,doi:10.1155/2018/9819360.
[35]Zaitseva O O,PoleZhaeva T V,Khudvakov A N,et al.Application of pectin rrom Rauvolfia serpentina(L.)Benth to the cryopreservation of human leucocyte cell suspensions[J].Cryo Lett,2018,39(1):72-78.
[36]Khudyakov A N,Kuleshova L G,Zaitseva O O,et al.Effect of pectins on water crystallization pattern and integrity of cells during freezing[J].Biopreserv Biobank,2019,17(1):52-57.
[37]Bakhtiarpoor M M,Setorki M P,Kaffashian M R P.Effects of essential oil of Satureja bachtiarica Bunge in a rat model of reserpine-induced depression[J].Iran J Med Sci,2018,43(4):409-415.
[38]Peres F F,Levin R,Suiama M A,et al.Cannabidiol prevents motor and cognitive impairments induced by reserpine in rats[J].Front Pharmacol,2016,doi:10.3389/fphar.2016.00343.
[39]Bispo J M M,Melo J E C,Gois A M,et al.Sex differences in the progressive model of parkinsonism induced by reserpine in rats[J].Behav Brain Res,2019,doi:10.1016/j.bbr.2019.01.041.
[40]Leal P C,Bispo J M M,Engelberth R C G J,et al.Serotonergic dysfunction in a model of parkinsonism induced by reserpine[J].J Chem Neuroanat,2019,doi:10.1016/j.jchemneu.2018.12.011.
[41]Isyraqiah F,Kutty K,Durairajanayagam D,et al.Effect of reserpine on the expression of tumour promoter,tumour suppressor and ulcer healing genes in the stomach of female Sprague-Dawley rats[J].Int Med J,2019,26(1):2-6.
[42]Mossoba M E,Flynn T J,Vohra S,et al.Human kidney proximal tubule cells are vulnerable to the effects of Rauwolfia serpentina[J].Cell Biol Toxicol,2016,31(6):285-293.
[43]Barleben L,Panjikar S,Ruppert M,et al.Molecular architecture of strictosidine glucosidase:The gateway to the biosynthesis of the monoterpenoid indole alkaloid family[J].Plant Cell,2007,19(9):2886-2897.
[44]Ma X,Panjikar S,Koepke J,et al.The structure of Rauvolfia serpentina strictosidine synthase is a novel six-bladed beta-propeller fold in plant proteins[J].Plant Cell,2006,18(4):907-920.
[45]Stoeckigt J,Panjikar S.Structural biology in plant natural product biosynthesis--architecture of enzymes from monoterpenoid indole and tropane alkaloid biosynthesis[J].Nat Prod Rep,2007,24(6):1382-1400.
[46]Xia L,Ruppert M,Wang M,et al.Structures of alkaloid biosynthetic glucosidases decode substrate specificity[J].ACS Chem Biol,2012,7(1):226-234.
[47]St?ckigt J,Panjikar S,Ruppert M,et al.The molecular architecture of major enzymes from ajmaline biosynthetic pathway[J].Phytochem Rev,2007,6(1):15-34.
[48]Bayer A,Ma X,St?ckigt J.Acetyltransfer in natural product biosynthesis--functional cloning and molecular analysis of vinorine synthase[J].Bioorgan Med Chem,2004,12(10):2787-2795.
[49]Sun L,Chen Y,Rajendran C,et al.Crystal structure of perakine reductase,founding member of a novel aldo-keto reductase(AKR)subfamily that undergoes unique conformational changes during NADPH binding[J].J Biol Chem,2012,287(14):11213-11221.
[50]Sun L,Ruppert M,Sheludko Y,et al.Purification,cloning,functional expression and characterization of perakine reductase:The first example from the AKRenzyme family,extending the alkaloidal network of the plant Rauvolfia[J].Plant Mol Biol,2008,67(5):455-467.
[51]Dang T T,Franke J,Tatsis E C,et al.Dual catalytic activity of a cytochrome P450 controls bifurcation at a metabolic branch point of alkaloid biosynthesis in Rauwolfia serpentina[J].Angew Chem Int Ed Engl,2017,56(32):9440-9444.
[52]Pasquali G,Porto D D,Fettneto A G.Metabolic engineering of cell cultures versus whole plant complexity in production of bioactive monoterpene indole alkaloids:Recent progress related to old dilemma[J].JBiosci Bioeng,2006,101(4):287-296.
[53]Kutchan T M,Hampp N,Lottspeich F,et al.The cDNAclone for strictosidine synthase from Rauvolfia serpentina.DNA sequence determination and expression in Escherichia coli[J].Febs Lett,1988,237(7):40-44.
[54]Gantet P,Memelink J.Transcription factors:Tools to engineer the production of pharmacologically active plant metabolites[J].Trends Pharmacol Sci,2002,23(12):563-569.
[55]Pauw B,Hilliou F A O,Martin V S,et al.Zinc finger proteins act as transcriptional repressors of alkaloid biosynthesis genes in Catharanthus roseus[J].J Biol Chem,2004,279(51):52940-52948.
[56]Prakash P,Rajakani R,Gupta V.Transcriptome-wide identification of Rauvolfia serpentina micro RNAs and prediction of their potential targets[J].Comput Biol Chem,2016,doi:10.1016/j.compbiolchem.2015.12.002.
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