糖基转移酶活性供体UDP-糖的生物合成及循环再生
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摘要
UDP-糖基供体依赖的糖基转移酶(UGTs)能够高效且特异性地催化多种天然产物及药物的糖基化修饰,从而达到提高水溶性、增加稳定性及改善生物活性的目的。但是,UGTs催化的糖基化反应需要使用价格昂贵且稳定性差的UDP-糖基供体,如UDP-葡萄糖、UDP-半乳糖等,这严重限制了UGTs的工业化应用。研究人员通过构建多酶级联催化体系以及改造体内代谢途径,能有效提高UDP-糖基供体的生物合成及再生效率,在一定程度上减少或避免了反应体系中外源UDP-糖的使用。该文概述了糖基化反应中UDP-糖基供体生物合成及循环再生策略的研究进展,从而为UGTs的规模化应用及新型糖苷类化合物的生物合成提供参考与借鉴。
UDP-sugar donor dependent glycosyltransferases( UGTs) catalyze the glycosylation of various natural products to improve the water solubility,stabilities and biological activities with high efficiency and specificity. However,the process requires large amount of UDP-activated sugar donors,such as UDP-glucose and UDP-galactose,of which the high prices and low stabilities limited the industrial application of UGTs. Recently,by constructing a multi-enzyme cascade catalytic system and engineering the metabolic pathway in vivo,the biosynthesis and regeneration of UDP-sugars can be effectively improved,thereby reducing or eliminating the addition of exogenous UDP-sugars in the reaction system. In this review,the authors have summarized the strategy of UDP-sugar donor biosynthesis and regeneration in glycosylation to provide a general perspective on large-scale application of UGTs and synthesis of novel glycoside compounds.
UDP-sugar donor dependent glycosyltransferases( UGTs) catalyze the glycosylation of various natural products to improve the water solubility,stabilities and biological activities with high efficiency and specificity. However,the process requires large amount of UDP-activated sugar donors,such as UDP-glucose and UDP-galactose,of which the high prices and low stabilities limited the industrial application of UGTs. Recently,by constructing a multi-enzyme cascade catalytic system and engineering the metabolic pathway in vivo,the biosynthesis and regeneration of UDP-sugars can be effectively improved,thereby reducing or eliminating the addition of exogenous UDP-sugars in the reaction system. In this review,the authors have summarized the strategy of UDP-sugar donor biosynthesis and regeneration in glycosylation to provide a general perspective on large-scale application of UGTs and synthesis of novel glycoside compounds.
引文
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[27]Simkhada D,Kurumbang N P,Lee H C,et al.Exploration of glycosylated flavonoids from metabolically engineered E.coli[J].Biotechnol Bioprocess Engin,2010,15(5):754-760.
[28]Xia T,Eiteman MA.Quercetin glucoside production by engineered Escherichia coli[J].Appl Biochem Biotechnol,2017,182(4):1358-1370.
[29]Parajuli P,Pandey R P,Trang N T H,et al.Synthetic sugar cassettes for the efficient production of flavonol glycosides in Escherichia coli[J].Microbial Cell Factories,2015,14(1):76.
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[31]De Bruyn F,De Paepe B,Maertens J,et al.Development of an in vivo glucosylation platform by coupling production to growth:Production of phenolic glucosides by a glycosyltransferase of Vitis vinifera[J].Biotechnol Bioengin,2015,112(8):1594-1603.
[32]Li Y,Li Y,Wang Y,et al.Production of rebaudioside A from stevioside catalyzed by the engineered Saccharomyces cerevisiae[J].Appl Biochem Biotechnol,2016,178(8):1586-1598.
[2]Liang H,Hu Z,Zhang T,et al.Production of a bioactive unnatural ginsenoside by metabolically engineered yeasts based on a new UDP-glycosyltransferase from Bacillus subtilis[J].Metabolic Engin,2017,44:60-69.
[3]Chu L L,Pandey R P,Lim H N,et al.Synthesis of umbelliferone derivatives in Escherichia coli and their biological activities[J].JBiolog Engin,2017,11(1):15.
[4]Chu L L,Pandey R P,Shin J Y,et al.Synthetic analog of anticancer drug daunorubicin from daunorubicinone using one-pot enzymatic UDP-recycling glycosylation[J].J Molec Catal B:Enzym,2016,124:1-10.
[5]费理文,王勇.甜味剂莱鲍迪苷D的高效生物催化合成[J].食品与发酵工业,2018,44(4):1-7.
[6]Wang Y,Chen L,Li Y,et al.Efficient enzymatic production of rebaudioside A from stevioside[J].Biosci,Biotechnol,Biochem,2016,80(1):67-73.
[7]吴旭日,陈依军,金月.一种莱鲍迪苷KA的制备方法[P].中国专利:CN107164435A,2017-09-15.
[8]Guleria P,Yadav S K.Overexpression of a glycosyltransferase gene SrUGT74G1 from Stevia improved growth and yield of transgenic Arabidopsis by catechin accumulation[J].Molec Biol Reports,2014,41(3):1741-1752.
[9]Muschiol J,Peters C,Oberleitner N,et al.Cascade catalysis-strategies and challenges en route to preparative synthetic biology[J].Chem Commun,2015,51(27):5798-5811.
[10]Ichikawa Y,Wang R,Wong C H.Regeneration of sugar nucleotide for enzymatic oligosaccharide synthesis[J].Methods Enzymol,1994,247:107-127.
[11]Noguchi T,Shiba T.Use of Escherichia coli polyphosphate kinase for oligosaccharide synthesis[J].Biosci,Biotechnol Biochem,1998,62(8):1594-1596.
[12]Chen X,Fang J,Zhang J,et al.Sugar nucleotide regeneration beads(Superbeads):A versatile tool for the practical synthesis of oligosaccharides[J].J American Chem Society,2001,123(9):2081-2082.
[13]Le T T,Pandey R P,Gurung R B,et al.Efficient enzymatic systems for synthesis of novelα-mangostin glycosides exhibiting antibacterial activity against Gram-positive bacteria[J].App Microbiol Biotechnol,2014,98(20):8527-8538.
[14]Shin J Y,Pandey R P,Jung H Y,et al.In vitro single-vessel enzymatic synthesis of novel Resvera-A glucosides[J].Carbohyd Res,2016,424:8-14.
[15]Pandey R P,Chu L L,Kim T-S,et al.Bioconversion of tetracycline antibiotics to novel glucoside derivatives by single-vessel multienzymatic glycosylation[J].J Microbiol Biotechnol,2018,28(2):298-304.
[16]Schm9lzer K,Gutmann A,Diricks M,et al.Sucrose synthase:Aunique glycosyltransferase for biocatalytic glycosylation process development[J].Biotechnol Adv,2016,34(2):88-111.
[17]Masada S,Kawase Y,Nagatoshi M,et al.An efficient chemoenzymatic production of small molecule glucosides with in situ UDP-glucose recycling[J].FEBS Lett,2007,581(13):2562-2566.
[18]Bungaruang L,Gutmann A,Nidetzky B.Leloir glycosyltransferases and natural product glycosylation:Biocatalytic synthesis of the C-glucoside nothofagin,a major antioxidant of redbush Herbal Tea[J].Adv Synthesis Cataly,2013,355(14-15):2757-2763.
[19]Huang F C,Hinkelmann J,Hermenau A,et al.Enhanced production ofβ-glucosides by in-situ UDP-glucose regeneration[J].JBiotechnol,2016,224:35-44.
[20]Son M H,Kim B G,Kim D H,et al.Production of flavonoid o-glucoside using sucrose synthase and flavonoid o-glucosyltransferase fusion protein[J].J Microbiol Biotechnol,2009,19(7):709-712.
[21]Diricks M,De Bruyn F,Van Daele P,et al.Identification of sucrose synthase in nonphotosynthetic bacteria and characterization of the recombinant enzymes[J].Appl Microbiol Biotechnol,2015,99(20):8465-8474.
[22]Schm9lzer K,Lemmerer M,Gutmann A,et al.Integrated process design for biocatalytic synthesis by a Leloir Glycosyltransferase:UDP-glucose production with sucrose synthase[J].Biotechnol Bioengin,2017,114(4):924-928.
[23]Diricks M,Gutmann A,Debacker S,et al.Sequence determinants of nucleotide binding in Sucrose Synthase:improving the affinity of a bacterial Sucrose Synthase for UDP by introducing plant residues[J].Protein Engin Design Selec,2017,30(3):143-150.
[24]Mao Z,Shin H-D,Chen R R.Engineering the E.coli UDP-glucose synthesis pathway for oligosaccharide synthesis[J].Biotechnol Progress,2006,22(2):369-374.
[25]Koizumi S,Endo T,Tabata K,et al.Large-scale production of UDP-galactose and globotriose by coupling metabolically engineered bacteria[J].Nature Biotechnol,1998,16(9):847-850.
[26]Thuan N H,Park J W,Sohng J K.Toward the production of flavone-7-O-β-d-glucopyranosides using Arabidopsis glycosyltransferase in Escherichia coli[J].Process Biochem,2013,48(11):1744-1748.
[27]Simkhada D,Kurumbang N P,Lee H C,et al.Exploration of glycosylated flavonoids from metabolically engineered E.coli[J].Biotechnol Bioprocess Engin,2010,15(5):754-760.
[28]Xia T,Eiteman MA.Quercetin glucoside production by engineered Escherichia coli[J].Appl Biochem Biotechnol,2017,182(4):1358-1370.
[29]Parajuli P,Pandey R P,Trang N T H,et al.Synthetic sugar cassettes for the efficient production of flavonol glycosides in Escherichia coli[J].Microbial Cell Factories,2015,14(1):76.
[30]Yang Y,Wang H-M,Tong Y-F,et al.Systems metabolic engineering of Escherichia coli to enhance the production of flavonoid glucuronides[J].RSC Adv,2016,6(40):33622-33630.
[31]De Bruyn F,De Paepe B,Maertens J,et al.Development of an in vivo glucosylation platform by coupling production to growth:Production of phenolic glucosides by a glycosyltransferase of Vitis vinifera[J].Biotechnol Bioengin,2015,112(8):1594-1603.
[32]Li Y,Li Y,Wang Y,et al.Production of rebaudioside A from stevioside catalyzed by the engineered Saccharomyces cerevisiae[J].Appl Biochem Biotechnol,2016,178(8):1586-1598.