Top

Published in:

2010 | OriginalPaper | Chapter

Chemoenzymatic and Bioenzymatic Synthesis of Carbohydrate Containing Natural Products

Authors : Bohdan Ostash, Xiaohui Yan, Victor Fedorenko, Andreas Bechthold

Published in: Natural Products via Enzymatic Reactions

Publisher: Springer Berlin Heidelberg

Activate our intelligent search to find suitable subject content or patents.

search-config

AI-assisted search

Off

Abstract

The domain of bioactive natural products contains many oligosaccharides and aglycones decorated with various sugars. Glycan moieties influence essential aspects of biology of small molecules, such as mode of action, target recognition, pharmacokinetics, stability, and others. Methods of generation of novel glycosylated natural products are therefore of great value, as they, for example, may help fight human diseases more efficiently or provide healthier diet. This review covers the existing literature published mainly over the last decade that deals with biology-based approaches to novel glycoforms. Both genetic manipulations of biosynthesis of glycoconjugates and chemoenzymatic synthesis of novel “sweet” molecules are reviewed here. Wherever available, relationships between carbohydrate portions of the natural products and their biological activities are highlighted.

Dont have a licence yet? Then find out more about our products and how to get one now:

Springer Professional "Wirtschaft+Technik"

Online-Abonnement

Mit Springer Professional "Wirtschaft+Technik" erhalten Sie Zugriff auf:

über 102.000 Bücher
über 537 Zeitschriften

aus folgenden Fachgebieten:

Automobil + Motoren
Bauwesen + Immobilien
Business IT + Informatik
Elektrotechnik + Elektronik
Energie + Nachhaltigkeit
Finance + Banking
Management + Führung
Marketing + Vertrieb
Maschinenbau + Werkstoffe
Versicherung + Risiko

Jetzt Wissensvorsprung sichern!

inform now

Springer Professional "Technik"

Online-Abonnement

Mit Springer Professional "Technik" erhalten Sie Zugriff auf:

über 67.000 Bücher
über 390 Zeitschriften

aus folgenden Fachgebieten:

Automobil + Motoren
Bauwesen + Immobilien
Business IT + Informatik
Elektrotechnik + Elektronik
Energie + Nachhaltigkeit
Maschinenbau + Werkstoffe

Jetzt Wissensvorsprung sichern!

inform now

previous chapter Enzymatic and Chemo-Enzymatic Approaches Towards Natural and Non-Natural Alkaloids: Indoles, Isoquinolines, and Others

next chapter Total (Bio)Synthesis: Strategies of Nature and of Chemists

Magnet S, Blanchard JS (2005) Molecular insights into aminoglycoside action and resistance. Chem Rev 105:477–497

Silver LL (2005) Does the cell wall of bacteria remain a viable source of targets for novel antibiotics. Biochem Pharmacol 71:996–1005

Dudareva N, Pichersky E (2008) Metabolic engineering of plant volatives. Curr Opin Biotechnol 19:181–189

Handelsman J (2004) Metagenomics: application of genomics to uncultured microorganisms. Microbiol Mol Biol Rev 68:669–685

Keller N, Turner G, Bennett JW (2005) Fungal secondary metabolism – from biochemistry to genomics. Nat Rev Microbiol 3:937–948

Kohanski MA, Dwyer DJ, Wierzbowski J et al (2008) Mistranslation of membrane proteins and two-component system activation trigger antibiotic mediated cell death. Cell 135:679–690

Laatsch H, Fotso S (2008) Naturally occurring anthracyclines. Top Curr Chem. doi:10.1007/128_2008_5

Patrick WM, Quandt EM, Swartzlander DB et al (2007) Multicopy suppression underpins metabolic evolvability. Mol Biol Evol 24:2716–2722

Wagner B, Sieber SA, Baumann M et al (2006) Solvent engineering substantially enhances the chemoenzymatic production of surfactin. ChemBioChem 7:595–597

10.

Thibodeaux CJ, Melançon CEI, H-w L (2008) Natural-product sugar biosynthesis and enzymatic glycodiversification. Angew Chem Int Ed Engl 47:9814–9859

11.

Thorson JS, Hosted TJ, Jiang J et al (2001) Nature's carbohydrate chemists: the enzymatic glycosylation of bioactive bacterial metabolites. Curr Org Chem 5:139–167

12.

Barton WA, Biggins JB, Jiang J et al (2002) Expanding pyrimidine diphosphosugar libraries via structure-based nucleotidylyltransferase engineering. Proc Natl Acad Sci USA 99:13397–13402

13.

Timmons SC, Jakeman DL (2007) Stereoselective chemical synthesis of sugar nucleotides via direct displacement of acylated glycosyl bromides. Org Lett 9:1227

14.

Marlow AL, Kiessling LL (2001) Improved chemical synthesis of UDP-galactofuranose. Org Lett 3:2517

15.

Wittmann V, Wong C-H (1997) ¹H-Tetrazole as catalyst in phosphomorpholidate coupling reactions: efficient synthesis of GDP-fucose, GDP-mannose, and UDP-galactose. J Org Chem 62:2144

16.

Jiang J, Biggins JB, Thorson JS (2000) A general enzymatic method for the synthesis of natural and “unnatural” UDP- and TDP-nucleotide sugars. J Am Chem Soc 122:6803–6804

17.

Salas JA, Méndez C (2005) Biosynthesis pathways for deoxysugars in antibiotic-producing actinomycetes: isolation, characterization and generation of novel glycosylated derivatives. J Mol Microbiol Biotechnol 9:77–85

18.

Yang J, Hoffmeister D, Liu L et al (2004) Natural product glycorandomization. Bioorg Med Chem 12:1577–1584

19.

Yang J, Fu X, Liao J et al (2005) Structure-based engineering of E. coli galactokinase as a first step toward in vivo glycorandomization. Chem Biol 12:657–664

20.

Blanchard S, Thorson JS (2006) Enzymatic tools for engineering natural product glycosylation. Curr Opin Chem Biol 10:263–271

21.

Thibodeaux CJ, Melancon CE, Liu HW (2007) Unusual sugar biosynthesis and natural product glycodiversification. Nature 446:1008–1016

22.

Farinas ET, Bulter T, Arnold FH (2001) Directed enzyme evolution. Curr Opin Biotechnol 12:545–551

23.

Tao H, Cornish VW (2002) Milestones in directed enzyme evolution. Curr Opin Chem Biol 6:858–864

24.

Jiang J, John BB, Jon ST (2001) Expanding the pyrimidine diphosphosugar repertoire: the chemoenzymatic synthesis of amino- and acetamidoglucopyranosyl derivatives13. Angew Chem Int Ed Engl 40:1502–1505

25.

Lavine JE, Cantlay E, Roberts C et al (1982) Purification and properties of galactokinase from Tetrahymena thermophila. Biochim Biophys Acta 717:76–85

26.

Dey PM (1983) Galactokinase of Vicia faba seeds. Eur J Biochem 136:155–159

27.

Thomas P, Bessell EM, Westwood JH (1974) The use of deoxyfluoro-d-galactopyranoses in a study of yeast galactokinase specificity. Biochem J 139:661–664

28.

Yang J, Fu X, Jia Q et al (2003) Studies on the substrate specificity of Escherichia coli galactokinase. Org Lett 5:2223–2226

29.

Debouck C, Riccio A, Schumperli D et al (1985) Structure of the galactokinase gene of Escherichia coli, the last gene of the gal operon. Nucleic Acids Res 13:1841–1853

30.

Hoffmeister D, Yang J, Liu L et al (2003) Creation of the first anomeric d/l-sugar kinase by means of directed evolution. Proc Natl Acad Sci USA 100:13184–13189

31.

Thoden JB, Holden HM (2003) Molecular structure of galactokinase. J Biol chem 278:33305–33311

32.

Yang J, Lesley L, Thorson JS (2004) Structure-based enhancement of the first anomericglucokinase. ChemBioChem 5:992–996

33.

Hoffmeister D, Thorson JS (2004) Mechanistic implications of Escherichia coli galactokinase structure-based engineering. ChemBioChem 5:989–992

34.

Kudo F, Kawabe K, Kuriki H et al (2005) A new family of glucose-1-phosphate/glucosamine-1-phosphate nucleotidylyltransferase in the biosynthetic pathways for antibiotics. J Am Chem Soc 127:1711–1718

35.

Murrell JM, Liu W, Shen B (2004) Biochemical characterization of the SgcA1 α-d-glucopyranosyl-1-phosphate thymidylyltransferase from the enediyne antitumor antibiotic C-1027 biosynthetic pathway and overexpression of sgcA1 in Streptomyces globisporus to improve C-1027 production. J Nat Prod 67:206–213

36.

Lennart L, Rudolf K, Peter RR et al (1993) Purification, characterization and HPLC assay of Salmonella glucose-1-phosphate thymidylyltransferase from the cloned rfbA gene. Eur J Biochem 211:763–770

37.

Blankenfeldt W, Asuncion M, Lam JS et al (2000) The structural basis of the catalytic mechanism and regulation of glucose-1-phosphate thymidylyltransferase (RmlA). EMBO J 19:6652–6663

38.

Jiang J, Christoph A, Thorson JS (2003) Application of the nucleotidylyltransferase E_p toward the chemoenzymatic synthesis of dTDP-desosamine analogues. ChemBioChem 4:443–446

39.

Thorson JS, William AB, Dirk H et al (2004) Structure-based enzyme engineering and its impact on in vitro glycorandomization. ChemBioChem 5:16–25

40.

Barton WA, Lesniak J, Biggins JB et al (2001) Structure, mechanism and engineering of a nucleotidylyltransferase as a first step toward glycorandomization. Nat Struct Mol Biol 8:545–551

41.

Zuccotti S, Zanardi D, Rosano C et al (2001) Kinetic and crystallographic analyses support a sequential-ordered bi-bi catalytic mechanism for Escherichia coli glucose-1-phosphate thymidylyltransferase. J Mol Biol 313:831–843

42.

Barton WA, Biggins JB, Jiang J et al (2002) Expanding pyrimidine diphosphosugar libraries via structure-based nucleotidylyltransferase engineering. Proc Natl Acad Sci USA 99:13397–13402

43.

Elling L (1995) Effect of metal ions on sucrose synthase from rice grains–a study on enzyme inhibition and enzyme topography. Glycobiology 5:201–206

44.

Zervosen A, Römer U, Elling L (1998) Application of recombinant sucrose synthase-large scale synthesis of ADP-glucose. J Mol Catal B Enzym 5:25–28

45.

Römer U, Nadja N, Köckenberger W et al (2001) Characterization of recombinant sucrose synthase 1 from potato for the synthesis of sucrose analogues. Adv Synth Catal 343:655–661

46.

Römer U, Schrader H, Günther N et al (2004) Expression, purification and characterization of recombinant sucrose synthase 1 from Solanum tuberosum L. for carbohydrate engineering. J Biotechnol 107:135–149

47.

Zervosen A, Elling L, Kula MR (1994) Continuous enzymatic synthesis of 2′-deoxy- thymidine-5′-α-(D-glucopyranosyl) diphosphate. Angew Chem Int Ed Engl 33:571–572

48.

Lavie A, Schlichting I, Vetter IR et al (1997) The bottleneck in AZT activation. Nat Med 3:922–924

49.

Zervosen A, Stein A, Adrian H et al (1996) Combined enzymatic synthesis of nucleotide (deoxy) sugars from sucrose and nucleoside monophosphates. Tetrahedron 52:2395–2404

50.

Johnson DA, H-w L (1998) Mechanisms and pathways from recent deoxysugar biosynthesis research. Curr Opin Chem Biol 2:642–649

51.

He X, Agnihotri G, H-w L (2000) Novel enzymatic mechanisms in carbohydrate metabolism. Chem Rev 100:4615–4662

52.

Liu H, Thorson JS (1994) Pathways and mechanisms in the biogenesis of novel deoxysugars by bacteria. Annu Rev Microbiol 48:223–256

53.

Sterner Rh, Liebl W (2001) Thermophilic adaptation of proteins. Crit Rev Biochem Mol Biol 36:39–106

54.

Zhang Z, Tsujimura M, J-i A et al (2005) Identification of an extremely thermostable enzyme with dual sugar-1-phosphate nucleotidylyltransferase activities from an acidothermophilic archaeon, Sulfolobus tokodaii strain 7. J Biol Chem 280:9698–9705

55.

Bae J, Kim K-H, Kim D et al (2005) A practical enzymatic synthesis of UDP sugars and NDP glucoses. ChemBioChem 6:1963–1966

56.

Mizanur RM, Pohl NLB (2009) Phosphomannose isomerase/GDP-mannose pyrophosphorylase from Pyrococcus furiosus: a thermostable biocatalyst for the synthesis of guanidinediphosphate-activated and mannose-containing sugar nucleotides. Org Biomol Chem 7:2135–2139

57.

Järvinen N, Mäki M, Räbinä J et al (2001) Cloning and expression of Helicobacter pylori GDP-l-fucose synthesizing enzymes (GMD and GMER) in Saccharomyces cerevisiae. Eur J Biochem 268:6458–6464

58.

Conklin PL, Norris SR, Wheeler GL et al (1999) Genetic evidence for the role of GDP-mannose in plant ascorbic acid (vitamin C) biosynthesis. Proc Natl Acad Sci USA 96:4198–4203

59.

Nao S, Yoshio N, Yasuo Y et al (2002) Guanosine diphosphate-4-keto-6-deoxy-d-mannose reductase in the pathway for the synthesis of GDP-6-deoxy-d-talose in Actinobacillus actinomycetemcomitans. Eur J Biochem 269:5963–5971

60.

Albermann C, Piepersberg W (2001) Expression and identification of the RfbE protein from Vibrio cholerae O1 and its use for the enzymatic synthesis of GDP-d-perosamine. Glycobiology 11:655–661

61.

Mäki M, Järvinen N, Räbinä J et al (2002) Functional expression of Pseudomonas aeruginosa GDP-4-keto-6-deoxy-d-mannose reductase which synthesizes GDP-rhamnose. Eur J Biochem 269:593–601

62.

Mizanur RM, Zea CJ, Pohl NL (2004) Unusually broad substrate tolerance of a heat-stable archaeal sugar nucleotidyltransferase for the synthesis of sugar nucleotides. J Am Chem Soc 126:15993–15998

63.

Endo T, Koizumi S (2000) Large-scale production of oligosaccharides using engineered bacteria. Curr Opin Struct Biol 10:536–541

64.

Koeller KM, Wong C-H (2000) Synthesis of complex carbohydrates and glycoconjugates: enzyme-based and programmable one-pot strategies. Chem Rev 100:4465–4494

65.

Rodríguez L, Aguirrezabalaga I, Allende N et al (2002) Engineering deoxysugar biosynthetic pathways from antibiotic-producing microorganisms: a tool to produce novel glycosylated bioactive compounds. Chem Biol 9:721–729

66.

Lombó F, Gibson M, Greenwell L et al (2004) Engineering biosynthetic pathways for deoxysugars: branched-chain sugar pathways and derivatives from the antitumor tetracenomycin. Chem Biol 11:1709–1718

67.

Méndez C, Salas JA (2002) Engineering glycosylation in bioactive compounds by combinatoiral biosynthesis. In: Wohlleben W (ed) Biocombinatorial approaches for drug finding, volume 51. Springer, Heidelberg

68.

Lombo F, Olano C, Salas JA et al (2009) Sugar biosynthesis and modification. In: Hopwood DA (ed) Methods in enzymology, vol 458. Academic Press, New York

69.

Salas JA, Méndez C (2007) Engineering the glycosylation of natural products in actinomycetes. Trends Microbiol 15:219–232

70.

Hertweck C, Luzhetskyy A, Rebets Y, Bechthold A (2007) Type II polyketide synthases: gaining a deeper insight into enzymatic teamwork. Nat Prod Rep 24:162–190

71.

Minotti G, Menna P, Salvatorelli E, Cairo G, Gianni L (2004) Anthracyclines: molecular advances and pharmacologic developments in antitumor activity and cardiotoxicity. Pharmacol Rev 56:185–229

72.

Madduri K, Kennedy J, Rivola G et al (1998) Production of the antitumor drug epirubicin (4’-epidoxorubicin) and its precursor by a genetically engineered strain of Streptomyces peucetius. Nat Biotechnol 16:69–74

73.

Raty K, Kunnari T, Hakala J et al (2000) A gene cluster from Streptomyces galilaeus involved in glycosylation of aclarubicin. Mol Gen Genet 264:164–172

74.

Torkell S, Kunnari T, Palmu K et al (2001) The entire nogalamycin biosynthetic gene cluster of Streptomyces nogalater: characterization of a 20-kb DNA region and generation of hybrid structures. Mol Genet Genomics 266:276–288

75.

Raty K, Hautala A, Torkkell S et al (2002) Characterization of mutations in aclacinomycin A-non-producing Streptomyces galilaeus strains with altered glycosylation patterns. Microbiology 148:3375–3384

76.

Lu W, Leimkuhler C, Oberthur M et al (2004) AknK is an L-2-deoxyfucosyltransferase in the biosynthesis of the anthracycline aclacinomycin A. Biochemistry 43:4548–4558

77.

Olano C, Abdelfattah MS, Gullon S et al (2008) Glycosylated derivatives of steffimycin: insights into the role of the sugar moieties for the biological activity. ChemBioChem 9:624–633

78.

Luzhetskyy A, Mayer A, Hoffmann J et al (2007) Cloning and heterologous expression of the aranciamycin biosynthetic gene cluster revealed a new flexible glycosyltransferase. ChemBioChem 8:599–602

79.

Luzhetskyy A, Hoffmann J, Pelzer S et al (2008) Aranciamycin analogs generated by combinatorial biosynthesis show improved antitumor activity. Appl Microbiol Biotechnol 80:15–19

80.

Garrido LM, Lombo F, Baig I et al (2006) Insights in the glycosylation steps during biosynthesis of the antitumor anthracycline cosmomycin: characterization of two glycycosyltransferase genes. Appl Microbiol Biotechnol 73:122–131

81.

Blanco G, Patallo EP, Brana AF et al (2001) Identification of a sugar flexible glycosyltransferase from Streptomyces olivaceus, the producer of the antitumor polyketide elloramycin. Chem Biol 8:253–263

82.

Perez M, Lombo F, Zhu L et al (2005) Combining sugar biosynthesis genes for the generation of l- and d-amicetose and formation of two novel antitumor tetracenomycins. Chem Commun 12:1604–1606

83.

Fischer C, Rodriguez L, Patallo EP et al (2002) Digitoxosyltetracenomycin C and glucosyltetracenomycin C, two novel elloramycin analogues obtained by exploring the sugar donor substrate specificity of glycosyltransferase ElmGT. J Nat Prod 65:1685–1689

84.

Lombo F, Menendez N, Salas JA et al (2006) The aureolic acid family of antitumor compounds: structure, mode of action, biosynthesis and novel derivatives. Appl Microbiol Biotechnol 73:1–14

85.

Perez M, Baig I, Brana AF et al (2008) Generation of new derivatives of the antitumor antibiotic mithramycin by altering the glycosylation pattern through combinatorial biosynthesis. ChemBioChem 9:2295–2304

86.

Rix U, Fischer C, Remsing LL et al (2002) Modification of post-PKS tailoring steps through combinatorial biosynthesis. Nat Prod Rep 19:542–580

87.

Wang L, White RL, Vining LC (2002) Biosynthesis of the dideoxysugar component in jadomycin B: genes in the jad cluster of Streptomyces venezuelae ISP5230 for l-digitoxose assembly and transfer to the angucycline aglycone. Microbiology 148:1091–1103

88.

Erb A, Luzhetskyy A, Bechthold A et al (2009) Cloning and sequencing of the biosynthetic gene cluster for saquayamycin Z and galtamycin B and the elucidation of the assembly of their saccharide chains. ChemBioChem 10:1392–1401

89.

Luzhetskyy A, Zhu L, Gibson M et al (2005) Generation of novel landomycins M and O through targeted gene disruption. ChemBioChem 6:675–678

90.

Luzhetskyy A, Vente A, Bechthold A (2005) Glycosyltransferases involved in the biosynthesis of biologically active natural products that contain oligosaccharides. Mol Biosyst 1:117–126

91.

Zhu L, Luzhetskyy A, Luzhetska M et al (2007) Generation of new landomycins with altered saccharide patterns through over-expression of the glycosyltransferase gene lanGT3 in the biosynthetic gene cluster of landomycin A in Streptomyces cyanogenus S-136. ChemBioChem 8:83–88

92.

Erb A, Krauth C, Luzhetskyy A et al (2009) Differences in substrate specificity of glycosyltransferases involved in landomycins A and E biosynthesis. Appl Microbiol Biotechnol 83:1067–1076

93.

Liu T, Kharel MK, Zhu L et al (2009) Inactivation of the ketoreductase gilU gene of the gilvocarvin biosynthetic gene cluster yields new analogues with partly improved biological activity. ChemBioChem 10:278–286

94.

Trefzer A, Hoffmeister D, Kunzel E et al (2000) Function of glycosyltransferase genes involved in urdamycin A biosynthesis. Chem Biol 7:133–142

95.

Kunzel E, Faust B, Oelkers C et al (1999) Inactivation of the urdGT2 gene, which encodes a glycosyltransferase responsible for the C-glycotransfer of activated d-olivose, leads to formation of the novel urdamycins I, J and K. J Am Chem Soc 121:11058–11062

96.

Trefzer A, Fischer C, Stockert S et al (2001) Elucidation of the function of two glycosyltransferase genes (lanGT1 and lanGT4) involved in landomycin biosynthesis and generation of new oligosaccharide antibiotics. Chem Biol 8:1239–1252

97.

Hoffmeister D, Weber M, Drager G et al (2004) Rational saccharide extension by using the natural product glycosyltransferase LanGT4. ChemBioChem 5:369–371

98.

Hoffmeister D, Wilkinson B, Foster G et al (2002) Engineered urdamycin glycosyltransferases are broadened and altered in substrate specificity. Chem Biol 9:287–295

99.

Hoffmeister D, Drager G, Ichinose K et al (2003) The C-glycosyltransferase UrdGT2 is unselective toward d- and l-configured nucleotide-bound rhodinose. J Am Chem Soc 125:4678–4679

100.

Borisova SA, Zhao L, Sherman DH et al (1999) Biosynthesis of desosamine: construction of a new macrolide carrying a genetically designed sugar moiety. Org Lett 1:133–136

101.

Yamase H, Zhao L, Liu H-W (2000) Engineering a hybrid sugar biosynthetic pathway: production of l-rhamnose and its implication on dihydrostreptose biosynthesis. J Am Chem Soc 122:12397–12398

102.

Melancon CE III, Yu WL, Liu HW (2005) TDP-mycaminose biosynthetic pathway revised and conversion of desosamine pathway to mycaminose pathway with one gene. J Am Chem Soc 127:12240–12241

103.

Melancon CE III, Liu HW (2007) Engineered biosynthesis of macrolide derivatives bearing the non-natural deoxysugars 4-epi-d-mycaminose and 3-N-methylamino-3-deoxy-d-fucose. J Am Chem Soc 129:4896–4899

104.

Hong JSJ, Park SH, Choi CY et al (2004) New olivosyl derivatives of methymycin/pikromycin from an engineered strain of Streptomyces venezuelae. FEMS Microbiol Lett 238:391–399

105.

Pageni BB, Oh TJ, Lee HC et al (2008) Metabolic engineering of noviose: heterologous expression of novWUS and generation of a new hybrid antibiotic, noviosylated 10-deoxymethynolide/narbonolide, from Streptomyces venezuelae YJ003-OTBP1. Biotechnol Lett 30:1609–1615

106.

Pageni BB, Oh TJ, Liou K et al (2008) Genetically engineered biosynthesis of macrolide derivatives including 4-amino-4, 6-dideoxy-l-glucose from Streptomyces venezuelae YJ003-OTBP3. J Microbiol Biotechnol 18:88–94

107.

Jung WS, Han AR, Hong JSJ et al (2007) Bioconversion of 12-, 14-, and 16-membered ring aglycones to glycosylated macrolides in an engineered strain of Streptomyces venezuelae. Appl Microbiol Biotechnol 76:1373–1381

108.

Butler AR, Bate N, Kiehl DE et al (2002) Genetic engineering of aminodeoxyhexose biosynthesis in Streptomyces fradiae. Nat Biotechnol 20:713–716

109.

Ziermann R, Betlach MC (1999) Recombinant polyketide synthesis in Streptomyces: engineering of improved host strains. Biotechniques 26:106–110

110.

Tang L, McDaniel R (2001) Construction of desosamine containing polyketide libraries using a glycosyltransferase with broad substrate specificity. Chem Biol 8:547–555

111.

Gaisser S, Lill R, Wirtz G et al (2001) New erythromycin derivatives from Saccharopolyspora erythraea using sugar O-methyltransferase from the spinosyn biosynthetic gene cluster. Mol Microbiol 41:1223–1231

112.

Gaisser S, Martin CJ, Wilkinson B et al (2002) Engineered biosynthesis of novel spinosyns bearing altered deoxyhexose substituents. Chem Commun 21:618–619

113.

Gaissser S, Carletti I, Schell U et al (2009) Glycosylation engineering of spinosyn analogues containing an l-olivose moiety. Org Biomol Chem 7:1705–1708

114.

Schell U, Haydock SF, Kaja AL et al (2008) Engineered biosynthesis of hybrid macrolide polyketides containing d-angolosamine and d-mycaminose moieties. Org Biomol Chem 6:3315–3327

115.

Martin JF, Aparicio JF (2009) Enzymology of the polyenes pimaricin and candicidin biosynthesis. Methods Enzymol 459:215–242

116.

Bruheim P, Borgos SEF, Tsan P et al (2004) Chemical diversity of polyene macrolides produced by Streptomyces noursei ATCC11455 and recombinant strain ERD44 with genetically altered polyketide synthase nysC. Antimicrob Agents Chemother 48:4120–4129

117.

Nedal A, Sletta H, Brautaset T et al (2007) Analysis of the mycosamine biosynthesis and attachment genes in the nystatin biosynthetic gene cluster of Streptomyces noursei ATCC11455. Appl Environ Microbiol 73:7400–7407

118.

Preobrazhenskaya MN, Olsufyeva EN, Solovieva SE et al (2009) Chemical modification and biological evaluation of new semisynthetic derivatives of 28, 29-didehydronystatin A1 (S44HP), a genetically engineered antifungal polyene macrolide antibiotic. J Med Chem 52:189–196

119.

Zotchev SB, Caffrey P (2009) Genetic analysis of nystatin and amphotericin biosynthesis. Methods Enzymol 459:243–258

120.

Chen S, Huang X, Zhou X et al (2003) Organizational and mutational analysis of a complete FR-008/candicidin gene cluster encoding a structurally related polyene complex. Chem Biol 10:1065–1076

121.

Rappa G, Shyam K, Lorico A et al (2000) Structure-activity studies of novobiocin analogs as modulators of the cytotoxicity of etoposide (VP-16). Oncol Res 12:113–119

122.

Heide L, Gust B, Anderle C et al (2008) Combinatorial biosynthesis, metabolic engineering and mutasynthesis for the generation of new aminocoumarin antibiotics. Curr Top Med Chem 8:667–679

123.

Freitag A, Rapp H, Heide L et al (2005) Metabolic engineering of aminocoumarins: inactivation of the methyltransferase gene cloP and generation of new clorobiocin derivatives in a heterologous host. ChemBioChem 6:1411–1418

124.

Freitag A, Li S-M, Heide L (2006) Biosynthesis of the unusual 5, 5-gem-dimethyl-deoxysugar noviose: investigation of the C-methyltransferase gene cloU. Microbiology 152:2433–2442

125.

Flatman RH, Eustaquio A, Li S-M et al (2006) Structure-activity relationships of aminocoumarin-type gyrase and topoisomerase IV inhibitors obtained by combinatorial biosynthesis. Antimicrob Agents Chemother 50:1136–1142

126.

Wolter F, Schoof S, Sussmuth R (2007) Synopsis of structural, biosynthetic, and chemical aspects of glycopeptide antibiotics. Top Curr Chem 267:143–185

127.

Fischbach M, Walsh CT (2006) Assembly-line enzymology for polyketide and nonribosomal peptide antibiotics: logic, machinery, and mechanisms. Chem Rev 106:3468–3496

128.

Kahne D, Leimkuhler C, Lu W et al (2005) Glycopeptide and lipoglycopeptide antibiotics. Chem Rev 105:405–428

129.

Galm U, Hager MH, Van Lanen SG et al (2005) Antitumor antibiotics: bleomycin, enediynes, and mitomycin. Chem Rev 105:739–758

130.

Sosio M, Stinchi S, Beltrametti F et al (2003) The gene cluster for the biosynthesis of the glycopeptide antibiotic A40926 by Nonomuraea species. Chem Biol 10:541–549

131.

Galm U, Wang L, Wendt-Pienkowski E et al (2008) In vitro manipulation of the bleomycin biosynthetic gene cluster in Streptomyces verticillus ATCC15003 revealing new insights into its biosynthetic pathway. J Biol Chem 283:28236–28245

132.

Wang L, Tao M, Wendt-Pienkowski E et al (2009) Functional characterization of tlmK unveiling unstable carbinolamide intermediates in the tallysomycin biosynthetic pathway. J Biol Chem 284:8256–8264

133.

Sanchez C, Mendez C, Salas JA (2006) Indolocarbazole natural products: occurrence, biosynthesis, and biological activity. Nat Prod Rep 23:1007–1045

134.

Sanchez C, Zhu L, Brana AF et al (2005) Combinatorial biosynthesis of antitumor indolocarbazole compounds. Proc Natl Acad Sci USA 102:461–466

135.

Salas AP, Zhu L, Sanchez C et al (2005) Deciphering the late steps in the biosynthesis of the anti-tumor indolocarbazole staurosporine: sugar donor substrate flexibility of the StaG glycosyltransferase. Mol Microbiol 58:17–27

136.

Sanchez C, Salas AP, Brana AF et al (2009) Generation of potent and selective kinase inhibitors by combinatorial biosynthesis of glycosylated indolocarbazoles. Chem Commun 4118–4120

137.

Weitnauer G, Hauser G, Hofmann C et al (2004) Novel avilamycin derivatives with improved polarity generated by targeted gene disruption. Chem Biol 11:1403–1411

138.

Hofmann C, Boll R, Heitmann B et al (2005) Genes encoding enzymes responsible for biosynthesis of l-lyxose and attachment of eurekanate during avilamycin biosynthesis. Chem Biol 12:1137–1143

139.

Treede I, Hauser G, Muhlenweg A et al (2005) Genes involved in formation and attachment of a two-carbon chain as a component of eurekanate, a branched-chain sugar moiety of avilamycin A. Appl Environ Microbiol 71:400–406

140.

Boll R, Hofmann C, Heitmann B et al (2006) The active conformation of avilamycin A is conferred by AviX12, a radical AdoMet enzyme. J Biol Chem 281:14756–14763

141.

Ostash B, Walker S (2005) Bacterial transglycosylase inhibitors. Curr Opin Chem Biol 9:456–459

142.

Ostash B, Saghatelian A, Walker S (2007) A streamlined metabolic pathway for the biosynthesis of moenomycin A. Chem Biol 14:257–267

143.

Yuan Y, Fuse S, Ostash B et al (2008) Structural analysis of the contacts anchoring moenomycin to peptidoglycan glycosyltransferases and implication for antibiotic design. ACS Chem Biol 3:429–436

144.

Ostash B, Doud E, Lin C et al (2009) Complete characterization of the seventeen step moenomycin biosynthetic pathway. Biochemistry 48:8830–8841

145.

Aharoni A, Giri AP, Deuerlein S et al (2003) Terpenoid metabolism in wild-type and transgenic Arabidopsis plants. Plant Cell 15:2866–2884

146.

Aharoni A, Jongsma MA, Kim TY et al (2006) Metabolic engineering of terpenoid biosynthesis in plants. Phytochem Rev 5:49–58

147.

Lu W, Leimkuhler C, Gatto GJ et al (2005) AknT is an activating protein for the glycosyltransferase AknS in l-aminodeoxysugar transfer to the aglycone of aclacinomycin A. Chem Biol 12:527–534

148.

Fujii I, Ebizuka Y (1997) Anthracycline biosynthesis in Streptomyces galilaeus. Chem Rev 97:2511–2524

149.

Temperini C, Messori L, Orioli P et al (2003) The crystal structure of the complex between a disaccharide anthracycline and the DNA hexamer d(CGATCG) reveals two different binding sites involving two DNA duplexes. Nucleic Acids Res 31:1464–1469

150.

Larsen AK, Escargueil AE, Skladanowski A (2003) Catalytic topoisomerase II inhibitors in cancer therapy. Pharmacol Ther 99:167–181

151.

Lu W, Leimkuhler C, Oberthur M et al (2004) AknK is an l-2-deoxyfucosyltransferase in the biosynthesis of the anthracycline aclacinomycin A. Biochemistry 43:4548–4558

152.

Lu W, Leimkuhler C, Gatto GJ et al (2005) AknT is an activating protein for the glycosyltransferase AknS in l-aminodeoxysugar transfer to the aglycone of aclacinomycin A. Chem Biol 12:527–534

153.

Weissman KJ, Leadlay PF (2005) Combinatorial biosynthesis of reduced polyketides. Nat Rev Microbiol 3:925–936

154.

Ogasawara Y, Katayama K, Minami A et al (2004) Cloning, sequencing, and functional analysis of the biosynthetic gene cluster of macrolactam antibiotic vicenistatin in Streptomyces halstedii. Chem Biol 11:79–86

155.

Quirós LM, Aguirrezabalaga I, Olano C et al (1998) Two glycosyltransferases and a glycosidase are involved in oleandomycin modification during its biosynthesis by Streptomyces antibioticus. Mol Microbiol 28:1177–1185

156.

Douthwaite S (2001) Structure-activity relationships of ketolides vs. macrolides. Clin Microbiol Infect 7:11–17

157.

Jenkins G, Cundliffe E (1991) Cloning and characterization of two genes from Streptomyces lividans that confer inducible resistance to lincomycin and macrolide antibiotics. Gene 108:55–62

158.

Quiros LM, Salas JA (1995) Biosynthesis of the macrolide oleandomycin by Streptomyces antibioticus. J Biol Chem 270:18234–18239

159.

Quiros LM, Carbajo RJ, Brana AF et al (2000) Glycosylation of macrolide antibiotics. Purification and kinetic studies of a macrolide glycosyltransferase from Streptomyces antibioticus. J Biol Chem 275:11713–11720

160.

Yang M, Proctor MR, Bolam DN et al (2005) Probing the breadth of macrolide glycosyltransferases: in vitro remodeling of a polyketide antibiotic creates active bacterial uptake and enhances potency. J Am Chem Soc 127:9336–9337

161.

Xu M, Zhou YN, Goldstein BP et al (2005) Cross-resistance of Escherichia coli RNA polymerases conferring rifampin resistance to different antibiotics. J Bacteriol 187:2783–2792

162.

Campbell EA, Pavlova O, Zenkin N et al (2005) Structural, functional, and genetic analysis of sorangicin inhibition of bacterial RNA polymerase. EMBO J 24:674–682

163.

Irschik H, Jansen R, Gerth K et al (1987) The sorangicins, novel and powerful inhibitors of eubacterial RNA ploymerase isolated from myxobacteria. J Antibiot 40:7–13

164.

Maren K, Carsten R, Herbert I et al (2007) SorF: a glycosyltransferase with promiscuous donor substrate specificity in vitro. ChemBioChem 8:813–819

165.

Geary TG (2005) Ivermectin 20 years on: maturation of a wonder drug. Trends Parasitol 21:530–532

166.

Luzhetskyy A, Fedoryshyn M, Dürr C et al (2005) Iteratively acting glycosyltransferases involved in the hexasaccharide biosynthesis of landomycin A. Chem Biol 12:725–729

167.

Zhang C, Albermann C, Fu X et al (2006) The in vitro characterization of the iterative avermectin glycosyltransferase AveBI reveals reaction reversibility and sugar nucleotide flexibility. J Am Chem Soc 128:16420–16421

168.

Francis TFT, Onkar MPS, Tadeusz S et al (1997) The high-resolution crystal structure of a 24-kDa gyrase B fragment from E. coli complexed with one of the most potent coumarin inhibitors, clorobiocin. Proteins Struct Funct Genet 28:41–52

169.

Steffensky M, Li S-M, Heide L (2000) Cloning, overexpression, and purification of novobiocic acid synthetase from Streptomyces spheroides NCIMB 11891. J Biol Chem 275:21754–21760

170.

Albermann C, Soriano A, Jiang J et al (2003) Substrate specificity of NovM: implications for novobiocin biosynthesis and glycorandomization. Org Lett 5:933–936

171.

Cooper RDG, Snyder NJ, Zweifel MJ et al (1996) Reductive alkylation of glycopeptide antibiotics: synthesis and antibacterial activity. J Antibiot 49:575–581

172.

Losey HC, Peczuh MW, Chen Z et al (2001) Tandem action of glycosyltransferases in the maturation of vancomycin and teicoplanin aglycones: novel glycopeptides. Biochemistry 40:4745–4755

173.

Solenberg PJ, Matsushima P, Stack DR et al (1997) Production of hybrid glycopeptide antibiotics in vitro and in Streptomyces toyocaensis. Chem Biol 4:195–202

174.

Fu X, Albermann C, Jiang J et al (2003) Antibiotic optimization via in vitro glycorandomization. Nat Biotechnol 21:1467–1469

175.

Losey HC, Jiang J, Biggins JB et al (2002) Incorporation of glucose analogs by GtfE and GtfD from the vancomycin biosynthetic pathway to generate variant glycopeptides. Chem Biol 9:1305–1314

176.

Norris EA, Thalia IN (2003) Mechanism of action of oritavancin and related glycopeptide antibiotics. FEMS Microbiol Rev 26:511–532

177.

Zhang C, Griffith BR, Fu Q et al (2006) Exploiting the reversibility of natural product glycosyltransferase-catalyzed reactions. Science 313:1291–1294

178.

Zhang C, Bitto E, Goff RD et al (2008) Biochemical and structural insights of the early glycosylation steps in calicheamicin biosynthesis. Chem Biol 15:842–853

179.

Kren V, Martínková L (2001) Glycosides in medicine: “the role of glycosidic residue in biological activity”. Curr Med Chem 8:1313–1338

180.

D'Auria JC, Gershenzon J (2005) The secondary metabolism of Arabidopsis thaliana: growing like a weed. Curr Opin Plant Biol 8:308–316

181.

Halliwell B, Rafter J, Jenner A (2005) Health promotion by flavonoids, tocopherols, tocotrienols, and other phenols: direct or indirect effects? antioxidant or not? Am J Clin Nutr 81:268S–276S

182.

Offen W, Martinez-Fleites C, Yang M et al (2006) Structure of a flavonoid glucosyltransferase reveals the basis for plant natural product modification. EMBO J 25:1396–1405

183.

Gantt RW, Goff RD, Williams GJ et al (2008) Probing the aglycon promiscuity of an engineered glycosyltransferase13. Angew Chem Int Ed Engl 47:8889–8892

184.

Hernández C, Olanoa C, Méndeza C et al (1993) Characterization of a Streptomyces antibioticus gene cluster encoding a glycosyltransferase involved in oleandomycin inactivation. Gene 134:139–140

185.

Williams GJ, Thorson JS (2008) A high-throughput fluorescence-based glycosyltransferase screen and its application in directed evolution. Nat Protoc 3:357–362

186.

Zachara NE, Hart GW (2002) The emerging significance of O-GlcNAc in cellular regulation. Chem Rev 102:431–438

187.

Helenius A, Aebi M (2001) Intracellular functions of N-linked glycans. Science 291:2364–2369

188.

Daniels MA, Hogquist KA, Jameson SC (2002) Sweet 'n' sour: the impact of differential glycosylation on T cell responses. Nat Immunol 3:903–910

189.

Alper J (2003) Glycobiology: turning sweet on cancer. Science 301:159–160

190.

Franz AH, Gross PH, Samoshin VV (2009) ChemInform abstract: syntheses of small cluster oligosaccharide mimetics. ChemInform. doi:10.1002/chin.200915274

191.

Mehta S, Andrews JS, Svensson B et al (2002) Synthesis and enzymic activity of novel glycosidase inhibitors containing sulfur and selenium. J Am Chem Soc 117:9783–9790

192.

Yuasa H, Hindsgaul O, Palcic MM (2002) Chemical-enzymic synthesis of 5′-thio-N-acetyllactosamine: the first disaccharide with sulfur in the ring of the non-reducing sugar. J Am Chem Soc 114:5891–5892

193.

Tsuruta O, Shinohara G, Yuasa H et al (1997) UDP-N-acetyl-5-thio-galactosamine is a substrate of lactose synthase. Bioorg Med Chem Lett 7:2523–2526

194.

Li TL, Huang F, Haydock SF et al (2004) Biosynthetic gene cluster of the glycopeptide antibiotic teicoplanin: characterization of two glycosyltransferases and the key acyltransferase. Chem Biol 11:107–119

195.

Dong SD, Oberthur M, Losey HC et al (2002) The structural basis for induction of VanB resistance. J Am Chem Soc 124:9064–9065

196.

Sosio M, Stinchi S, Beltrametti F et al (2003) The gene cluster for the biosynthesis of the glycopeptide antibiotic A40926 by Nonomuraea species. Chem Biol 10:541–549

197.

Kruger RG, Lu W, Oberthür M et al (2005) Tailoring of glycopeptide scaffolds by the acyltransferases from the teicoplanin and A-40, 926 biosynthetic operons. Chem Biol 12:131–140

198.

Ge M, Chen Z, Onishi HR et al (1999) Vancomycin derivatives that inhibit peptidoglycan biosynthesis without binding D-Ala-D-Ala. Science 284:507–511

199.

Kerns R, Dong SD, Fukuzawa S et al (2000) The role of hydrophobic substituents in the biological activity of glycopeptide antibiotics. J Am Chem Soc 122:12608–12609

200.

Malabarba A, Ciabatti R (2001) Glycopeptide derivatives. Curr Med Chem 8:1759–1773

201.

Malabarba A, Nicas TI, Thompson RC (1997) Structural modifications of glycopeptide antibiotics. Med Res Rev 17:69–137

202.

Zhang C, Albermann C, Fu X et al (2006) RebG- and RebM-catalyzed indolocarbazole diversification. ChemBioChem 7:795–804

203.

Rodriguez L, Rodriguez D, Olano C et al (2001) Functional analysis of OleY l-oleandrosyl 3-O-methyltransferase of the oleandomycin biosynthetic pathway in Streptomyces antibioticus. J Bacteriol 183:5358–5363

204.

Bauer NJ, Kreuzman AJ, Dotzlaf JE et al (1988) Purification, characterization, and kinetic mechanism of S-adenosyl-l- methionine: macrocin O-methyltransferase from Streptomyces fradiae. J Biol Chem 263:15619–15625

205.

Kreuzman AJ, Turner JR, Yeh WK (1988) Two distinctive O-methyltransferases catalyzing penultimate and terminal reactions of macrolide antibiotic (tylosin) biosynthesis. Substrate specificity, enzyme inhibition, and kinetic mechanism. J Biol Chem 263:15626–15633

206.

Masaharu I, Hideaki S, Yoshio T et al (1994) A gene encoding mycinamicin III O-methyltransferase from Micromonospora griseorubida. Gene 141:121–124

207.

Meyers CLF, Oberthür M, Heide L et al (2004) Assembly of dimeric variants of coumermycins by tandem action of the four biosynthetic enzymes CouL, CouM, CouP, and NovN. Biochemistry 43:15022–15036

208.

Pi N, Meyers CLF, Pacholec M et al (2004) Mass spectrometric characterization of a three-enzyme tandem reaction for assembly and modification of the novobiocin skeleton. Proc Natl Acad Sci USA 101:10036–10041

209.

Zhang C, Weller RL, Thorson JS et al (2006) Natural product diversification using a non-natural cofactor analogue of S-adenosyl-L-methionine. J Am Chem Soc 128:2760–2761

210.

Balibar CJ, Garneau-Tsodikova S, Walsh CT (2007) Covalent CouN7 enzyme intermediate for acyl group shuttling in aminocoumarin biosynthesis. Chem Biol 14:679–690

211.

Fridman M, Balibar CJ, Lupoli T et al (2007) Chemoenzymatic formation of novel aminocoumarin antibiotics by the enzymes CouN1 and CouN7. Biochemistry 46:8462–8471

212.

Ramos A, Olano C, Brana AF et al (2009) Modulation of deoxysugar transfer by the elloramycin glycosyltransferase ElmGT through site-directed mutagenesis. J Bacteriol 191:2871–2875

213.

Aharoni A, Thieme K, Chiu CPC et al (2006) High-throughput methodology for the directed evolution of glycosyltransferases. Nat Methods 3:609–614

214.

Ahmed A et al (2006) Colchicine glycorandomization influences cytotoxicitiy and mechanism of action. J Am Chem Soc 128:14224–14225

215.

Durr C, Hoffmeister D, Wohlert SE et al (2004) The glycosyltransferase UrdGT2 catalyzes both C- and O-glycosidic sugar transfers. Angew Chem Int Ed 43:2962–2965

216.

Mayer C, Jakeman DL, Mah M et al (2001) Directed evolution of new glycosynthases from Agrobacterium β-glucosidase: a general screen to detect enzymes for oligosaccharide synthesis. Chem Biol 8:437–443

217.

Williams GJ, Zhang C, Thorson JS (2007) Expanding the promiscuity of natural-product glycosyltransferase by directed evolution. Nat Chem Biol 3:657–662

218.

Persson M, Palcic MM (2008) A high-throughput pH indiciator assay for screening glycosyltransferase saturation mutagenesis libraries. Anal Biochem 378:1–7

219.

Lee HY, Khosla C (2007) Bioassay-guided evolution of glycosylated macrolide antibiotics in Escherichia coli. PLoS Biol 5:0243–0250

220.

Xia G, Chen L, Sera T et al (2002) Directed evolution of novel polymerase activities: mutation of a DNA polymerase into an efficient RNA polymerase. Proc Natl Acad Sci USA 99:6597–6602

221.

Love KR, Swoboda JG, Noren CJ et al (2006) Enabling glycosyltransferase evolution: a facile substrate-attachment strategy for phage-display enzyme evolution. ChemBioChem 7:753–756

Title: Chemoenzymatic and Bioenzymatic Synthesis of Carbohydrate Containing Natural Products
Authors: Bohdan Ostash
Xiaohui Yan
Victor Fedorenko
Andreas Bechthold
Publisher: Springer Berlin Heidelberg
Book: Natural Products via Enzymatic Reactions
Print ISBN: 978-3-642-16426-2

Electronic ISBN: 978-3-642-16427-9

Copyright Year: 2010
DOI: https://doi.org/10.1007/128_2010_78