人参皂苷糖基转移酶基因研究概述Overview of research in ginsenosides glycosyltransferase
林廷文;杜金法;黄丽瑾;陆续;
LIN Ting-wen;DU Jin-fa;HUANG Li-jin;LU Xu;State Key Laboratory of Natural Medicines, School of Traditional Chinese Pharmacy,China Pharmaceutical University;
摘要(Abstract):
糖基转移酶(UGTs)是人参皂苷生物合成中的关键酶,可催化糖基从供体分子转移到受体分子,形成各种具有生物活性的糖苷类化合物。随着高通量测序技术的发展,大量的药用植物基因组和转录组序列被解析,越来越多的UGTs基因得以发掘与验证。UGTs基因常见的发掘手段有差异表达分析、同源序列筛选、基因簇筛选、化学蛋白质组筛选等。该文总结了人参属3种名贵中药材三七、人参、西洋参中UGTs基因筛选和功能验证的研究进展,为天然产物中UGTs基因的研究提供参考。
Glycosyltransferases(UGTs) are key enzymes in the biosynthesis of ginsenosides, which can catalyze the transfer of glycans from donor molecules to acceptor molecules, and form a variety of biologically active glycoside compounds. With the development of high-throughput sequencing technology, a large number of medicinal plant genome and transcriptome sequences have been catalyzed, while more and more UGT genes have been discovered and verified. The methods of discovering UGT genes include differential expression analysis, homologous sequence screening, gene cluster screening, chemical proteome screening. This paper summarized the research progress of UGT genes screening and functional verification of three valuable Panax medicinal materials P. notoginseng, P. ginseng, and P. quinquefolius, so as to provide a reference for the study of UGT genes in natural products.
关键词(KeyWords):
人参皂苷;糖基转移酶;生物合成;基因筛选
ginsenosides;glycosyltransferase;biosynthesis;gene screening
基金项目(Foundation): 国家重点研发计划项目(2019YFC1711000);; 国家自然科学基金项目(81973414);; 江苏省研究生研究与实践创新计划项目(KYCX19_0650)
作者(Author):
林廷文;杜金法;黄丽瑾;陆续;
LIN Ting-wen;DU Jin-fa;HUANG Li-jin;LU Xu;State Key Laboratory of Natural Medicines, School of Traditional Chinese Pharmacy,China Pharmaceutical University;
Email:
DOI: 10.19540/j.cnki.cjcmm.20200508.602
参考文献(References):
- [1] YUAN C S,WANG C Z,WICKS S M,et al.Chemical and pharmacological studies of saponins with a focus on American ginseng[J].J Gins Res,2011,34(3):160.
- [2] QI L W,WANG C Z,YUAN C S.Ginsenosides from American ginseng:chemical and pharmacological diversity[J].Phytoche-mistry,2011,72(8):689.
- [3] RADAD K,MOLDZIO R,RAUSCH W D.Ginsenosides and their CNS targets[J].CNS Neurosci Ther,2011,17(6):761.
- [4] KIM Y J,ZHANG D,YANG D C.Biosynthesis and biotechnological production of ginsenosides [J].Biotechnol Adv,2015,33(6):717.
- [5] CHRISTENSEN L P.Ginsenosides chemistry,biosynthesis,ana-lysis,and potential health effects[J].Adv Food Nutr Res,2009,55(55):1.
- [6] YNAG W Z,HU Y,WU W Y,et al.Saponins in the genus Panax L.(Araliaceae):a systematic review of their chemical diversity[J].Phytochemistry,2014,106:7.
- [7] WAN J B,LI S,CHEN J M,et al.Chemical characteristics of three medicinal plants of the Panax genus determined by HPLC-ELSD[J].J Sep Sci,2007,30(6):825.
- [8] BARVKAR V T,PARDESHI V C,KALE S M,et al.Phylo-genomic analysis of UDP glycosyltransferase 1 multigene family in Linum usitatissimum identified genes with varied expression patterns[J].BMC genomics,2012,13(1):175.
- [9] BRAZIER-HICKS M,GERSHATER M,DIXON D,et al.Substrate specificity and safener inducibility of the plant UDP-glucose-dependent family 1 glycosyltransferase super family[J].Plant Biotechnol J,2018,16(1):337.
- [10] LEE M H,JEONG J H,SEO J W,et al.Enhanced triterpene and phytosterol biosynthesis in Panax ginseng overexpressing squalene synthase gene[J].Plant Cell Physiol,2004,45(8):976.
- [11] HAN J Y,IN J G,KWON Y S,et al.Regulation of ginsenoside and phytosterol biosynthesis by RNA interferences of squalene epo-xidase gene in Panax ginseng[J].Phytochemistry,2010,71(1):36.
- [12] LEE M H,HAN J Y,KIM H J,et al.Dammarenediol-II production confers TMV tolerance in transgenic tobacco expressing Panax ginseng dammarenediol-Ⅱ synthase[J].Plant Cell Physiol,2012,53(1):173.
- [13] HAN J Y,KIM H J,KWON Y S,et al.The CYP450 enzyme CYP716A47 catalyzes the formation of protopanaxadiol from dammarenediol-Ⅱ during ginsenoside biosynthesis in Panax ginseng[J].Plant Cell Physiol,2011,52(12):2062.
- [14] HAN J Y,HWANG H S,CHOI S W,et al.Cytochrome P450 CYP716A53v2 catalyzes the formation of protopanaxatriol from protopanaxadiol during ginsenoside biosynthesis in Panax ginseng[J].Plant Cell Physiol,2012,53(9):1535.
- [15] YANG J L,HU Z F,ZHANG T T,et al.Progress on the studies of the key enzymes of ginsenoside biosynthesis[J].Molecules,2018,23(3):589.
- [16] LAIRSON L L,HENRISSAT B,DAVIES G J,et al.Glycosyltransferases:structures,functions,and mechanisms[J].Annu Rev Biochem,2008,77(1):521.
- [17] CHANG A,SANGH S,PHILLIPS JR G N,et al.Glycosyltransferase structural biology and its role in the design of catalysts for glycosylation[J].Curr Opin Biotech,2011,22(6):800.
- [18] YAN X,FAN Y,WEI W,et al.Production of bioactive ginse-noside compound K in metabolically engineered yeast[J].Cell Res,2014,24(6):770.
- [19] YUE C J,ZHONG J J.Purification and characterization of UDPG:ginsenoside Rd glucosyl-transferase from suspended cells of Panax notoginseng[J].Process Biochem,2005,40(12):3742.
- [20] WEI W,WANG P,WEI Y,et al.Characterization of Panax ginseng UDP-glycosyl transferases catalyzing protopanaxatriol and biosyntheses of bioactive ginsenosides F1 and Rh1 in metabolically engineered yeasts[J].Mol Plant,2015,8(9):1412.
- [21] JUNG S C,KIM W,PARK S C,et al.Two ginseng UDP-glycosyltransferases synthesize ginsenoside Rg3 and Rd[J].Plant Cell Physiol,2014,55(12):2177.
- [22] LU C,ZHAO S,WEI G,et al.Functional regulation of ginse-noside biosynthesis by RNA interferences of a UDP-glycosyltransferase gene in Panax ginseng and Panax quinquefolius[J].Plant Physiol Biochem,2017,111:67.
- [23] LU C,ZHAO S J,WANG X S.Functional regulation of a UDP-glucosyltransferase gene (Pq3-O-UGT1) by RNA interference and overexpression in Panax quinquefolius[J].Plant Cell Tiss Org (PCTOC),2017,129(3):445.
- [24] 冯鹏程.西洋参 Pq-PPT-6,20-O-UGT 和 Pq-PPT-6-O-UGT 糖基转移酶基因的克隆与功能分析[D].长春:吉林大学,2019.
- [25] DAI Z,LIU Y,ZHANG X,et al.Metabolic engineering of Saccharomyces cerevisiae for production of ginsenosides[J].Metab Eng,2013,20:146.
- [26] WANG P,WEI Y,FAN Y,et al.Production of bioactive ginsenosides Rh2 and Rg3 by metabolically engineered yeasts[J].Metab Eng,2015,29:97.
- [27] CHEN S,LUO H,LI Y,et al.454 EST analysis detects genes putatively involved in ginsenoside biosynthesis in Panax ginseng[J].Plant Cell Rep,2011,30(9):1593.
- [28] RAHIMIS,KIM Y J,YANG D C.Production of ginseng saponins:elicitation strategy and signal transductions[J].Appl Microbiol Biot,2015,99(17):6987.
- [29] RAHIMI S,KIM Y J,DEVI B S,et al.Sodium nitroprusside enhances the elicitation power of methyl jasmonate for ginsenoside production in Panax ginseng roots[J].Res Chem Intermediat,2016,42(4):2937.
- [30] RAHIMI S,KIM Y J,SUKWEENADHI J,et al.PgLOX6 encoding a lipoxygenase contributes to jasmonic acid biosynthesis and ginsenoside production in Panax ginseng[J].J Exp Bot,2016,67(21):6007.
- [31] LI J,WANG J,WU X,et al.Jasmonic acid and methyl dihydrojasmonate enhance saponin biosynthesis as well as expression of functional genes in adventitious roots of Panax notoginseng FH Chen[J].Biotechnol Appl Bioc,2017,64(2):225.
- [32] KANG K B,JAYAKODI M,LEE Y S,et al.Identification of candidate UDP-glycosyltransferases involved in protopanaxadiol-type ginsenoside biosynthesis in Panax ginseng[J].Sci Rep-UK,2018,8(1):1.
- [33] HAYASHI H,HUANG P,INOUE K.Up-regulation of soyasaponin biosynthesis by methyl jasmonate in cultured cells of Glycyrrhiza glabra[J].Plant Cell Physiol,2003,44(4):404.
- [34] SHABANI L,EHSANPOUR A A,ASGHARI G,et al.Glycyrrhizin production by in vitro cultured Glycyrrhiza glabra elicited by methyl jasmonate and salicylic acid[J].Russ J Plant Physl,2009,56(5):621.
- [35] KIM O T,BANG K H,KIM Y C,et al.Upregulation of ginse-noside and gene expression related to triterpene biosynthesis in ginseng hairy root cultures elicited by methyl jasmonate[J].Plant Cell Tiss Org (PCTOC),2009,98(1):25.
- [36] KIM O T,YOO N H,KIM G S,et al.Stimulation of Rg3 ginse-noside biosynthesis in ginseng hairy roots elicited by methyl jasmonate[J].Plant Cell Tiss Org (PCTOC),2013,112(1):87.
- [37] KHOROLRAGCHAA A,KIM Y J,RAHIMI S,et al.Grouping and characterization of putative glycosyltransferase genes from Panax ginseng Meyer[J].Gene,2014,536(1):186.
- [38] SUI C,ZHANG J,WEI J,et al.Transcriptome analysis of Bupleurum chinense focusing on genes involved in the biosynthesis of saikosaponins[J].BMC Genomics,2011,12:539.
- [39] SUN C,LI Y,WU Q,et al.De novo sequencing and analysis of the American ginseng root transcriptome using GS FLX Titanium platform to discover putative genes involved in ginsenosides biosynthesis[J].BMC Genomics,2010,1:262.
- [40] LI Y,LUO H M,SUN C,et al.EST analysis reveals putative genes involved in glycyrrhizin biosynthesis[J].BMC Genomics,2010,11:268.
- [41] XU J,CHU Y,LIAO B,et al.Panax ginseng genome examination for ginsenoside biosynthesis[J].Gigascience,2017,6(11):gix093.
- [42] WNAG S,BAI H,CAI Z,et al.MALDI imaging for the localization of saponins in root tissues and rapid differentiation of three Panax herbs[J].Electrophoresis,2016,37(13):1956.
- [43] WEI G,YANG F,WEI F,et al.Metabolomes and transcriptomes revealed the saponin distribution in root tissues of Panax quinquefolius and Panax notoginseng[J].J Gins Res,2019,doi:10.10161/j.jgr.2019.05.009.
- [44] ZHAO Q,YANG J,CUI M Y,et al.The reference genome sequence of Scutellaria baicalensis provides insights into the evolution of wogonin biosynthesis[J].Mol Plant,2019,12(7):935.
- [45] GUO L,WINZER T,YANG X,et al.The opium poppy genome and morphinan production[J].Science,2018,362(6412):343.
- [46] WINZER T,GAZDA V,HE Z,et al.A Papaver somniferum 10-gene cluster for synthesis of the anticancer alkaloid noscapine[J].Science,2012,336(6089):1704.
- [47] ANASTASIA O,THOMAS L,MICHAEL J S,et al.A noncanonical vacuolar sugar transferase required for biosynthesis of antimicrobial defense compounds in oat[J].Proc Natl Acad Sci USA,2019,116(52):27105.
- [48] PADDON C J,WESTFALL P J,PITERA D J,et al.High-level semi-synthetic production of the potent antimalarial artemisinin[J].Nature,2013,496(7446):528.
- [49] GALANIE S,THODEY K,TRENCHARD I J,et al.Complete biosynthesis of opioids in yeast[J].Science,2015,349(6252):1095.
- [50] ZHUANG Y,YANG G Y,CHEN X,et al.Biosynthesis of plantderived ginsenoside Rh2 in yeast via repurposing a key promis-cuous microbial enzyme[J].Metab Eng,2017,42:25.
- [51] LU J,YAO L,LI J X,et al.Characterization of UDP-glycosyltransferase involved in biosynthesis of ginsenosides Rg1 and Rb1 and identification of critical conserved amino acid residues for its function[J].J Agr Food Chem,2018,66(36):9446.
- [52] ZHOU Y Q,LI W C,YOU W J,et al.Discovery of arabidopsis UGT73C1 as a steviol-catalyzing UDP-glycosyltransferase with chemical probes[J].Chem Commun,2018,54:7179.
- [53] LI W C,ZHOU Y Q,YOU W J,et al.Development of photoaffinity probe for the discovery of steviol glycosides biosynthesis pathway in Stevia rebuadiana and rapid substrate screening[J].ACS Chem Biol,2018,doi:10.1021/acschembio.8b00285.
- 林廷文
- 杜金法
- 黄丽瑾
- 陆续
LIN Ting-wen- DU Jin-fa
- HUANG Li-jin
- LU Xu
- State Key Laboratory of Natural Medicines
- School of Traditional Chinese Pharmacy
- China Pharmaceutical University
- 林廷文
- 杜金法
- 黄丽瑾
- 陆续
LIN Ting-wen- DU Jin-fa
- HUANG Li-jin
- LU Xu
- State Key Laboratory of Natural Medicines
- School of Traditional Chinese Pharmacy
- China Pharmaceutical University