Enzymatic tools for engineering natural product glycosylation

Current Opinion in Chemical Biology

Volumn 10, Issue 3, 2006, Pages 263-271

  Blanchard, Sophie ^a   Thorson, Jon S ^a  

^a UNIVERSITY OF WISCONSIN MADISON   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AGLYCONE; AVILAMYCIN; GLYCOSYLTRANSFERASE; NUCLEOSIDE DIPHOSPHATE KINASE; NUCLEOTIDE; PENTOSE; SUGAR; VANCOMYCIN DERIVATIVE;

ACTINOMADURA; BIOLOGICAL ACTIVITY; BIOSYNTHESIS; CHEMICAL REACTION; CHEMICAL STRUCTURE; DEOXYGENATION; ENZYME GLYCOSYLATION; GENE CLUSTER; GENE DELETION; GLYCOSYLATION; MASS SPECTROMETRY; NONHUMAN; PROTEIN ENGINEERING; REVIEW; STREPTOMYCES; STREPTOMYCES FRADIAE; STREPTOMYCES VENEZUELAE; SYNTHESIS;

BIOLOGICAL PRODUCTS; COMBINATORIAL CHEMISTRY TECHNIQUES; ENZYMES; GLYCOSYLATION;

EID: 33744523569     PISSN: 13675931     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.cbpa.2006.04.001     Document Type: Review

References (52)

1. Newman D.J., Cragg G.M., and Snader K.M. Natural products as sources of new drugs over the period 1981-2002. J Nat Prod 66 (2003) 1022-1037
2. Weymouth-Wilson A.C. The role of carbohydrates in biologically active natural products. Nat Prod Rep 14 (1997) 99-110
3. Zhang G., Shen J., Cheng H., Zhu L., Fang L., Luo S., Muller M.T., Lee G.E., Wei L., Du Y., et al. Syntheses and biological activities of rebeccamycin analogs with uncommon sugars. J Med Chem 48 (2005) 2600-2611. Reports the total syntheses of rebbecamycin analogs containing uncommon sugars and substitutions on the imide nitrogen. Some rebbecamycin derivatives with uncommon sugars showed distinct cytotoxicities and topo I targeting activities. This study implicates the sugar structure, especially the 2-OH and 6-OH groups, as a key element for the activity of rebbecamycin and glycosylated derivatives.
4. Zhu L., Cao X., Chen W., Zhang G., Sun D., and Wang P.G. Syntheses and biological activities of daunorubicin analogs with uncommon sugars. Bioorg Med Chem 13 (2005) 6381-6387
5. Elchert B., Li J., Wang J., Hui Y., Rai R., Ptak R., Ward P., Takemoto J.Y., Bensaci M., and Chang C.-W.T. Application of the synthetic amino sugars for glyco-diversification: synthesis and antimicrobial studies of pyranmycin. J Org Chem 69 (2004) 1513-1523
6. Fu X., Albermann C., Zhang C., and Thorson J.S. Diversifying vancomycin via chemoenzymatic strategies. Org Lett 7 (2005) 1513-1515
7. +-ATPase inhibition.
8. Langenhan J.M., Griffith B.R., and Thorson J.S. Neoglycorandomization and chemoenzymatic glycorandomization: two complementary tools for natural product diversification. J Nat Prod 68 (2005) 1696-1711
9. Griffith B.R., Langenhan J.M., and Thorson J.S. 'Sweetening' natural products via glycorandomization. Curr Opin Biotechnol 16 (2005) 622-630. This report highlights recent advances relevant to two complementary glycorandomization strategies. Chemoenzymatic glycorandomization is a biocatalytic approach dependent upon the substrate promiscuity of enzymes to activate and attach sugars to natural products. Neoglycorandomization is an efficient one-step chemical sugar ligation reaction that does not require prior sugar protection or activation.
10. Rupprath C., Schumacher T., and Elling L. Nucleotide deoxysugars: essential tools for the glycosylation engineering of novel bioactive compounds. Curr Med Chem 12 (2005) 1637-1675. This review provides a survey of the synthesis of TDP-activated sugars by chemical and chemoenzymatic approaches and discusses the promiscuity of glycosyltransferases. It summarizes the most important enzymes in the field of synthesis using enzymes from biosynthetic pathways.
11. He X.M., and Liu H.-W. Formation of unusual sugars: mechanistic studies and biosynthetic applications. Annu Rev Biochem 71 (2002) 701-754
12. Freel Meyers C.L., Oberthuer M., Xu H., Heide L., Kahne D., and Walsh C.T. Characterization of NovP and NovN: completion of novobiocin biosynthesis by sequential tailoring of the noviosyl ring. Angew Chem Int Ed Engl 43 (2004) 67-70
13. Menendez N., Nur-e-Alam M., Brana A.F., Rohr J., Salas J.A., and Mendez C. Tailoring modification of deoxysugars during biosynthesis of the antitumor drug chromomycin A3 by Streptomyces griseus ssp. griseus. Mol Microbiol 53 (2004) 903-915
14. Salas J.A., and Mendez C. Biosynthesis pathways for deoxysugars in antibiotic-producing actinomycetes: isolation, characterization and generation of novel glycosylated derivatives. J Mol Microbiol Biotechnol 9 (2005) 77-85
15. He X., and Liu H.-w. Mechanisms of enzymatic C-O bond cleavages in deoxyhexose biosynthesis. Curr Opin Chem Biol 6 (2002) 590-597
16. Szu P.-h., He X., Zhao L., and Liu H.-w. Biosynthesis of TDP-D-desosamine: identification of a strategy for C4 deoxygenation. Angew Chem Int Ed Engl 44 (2005) 6742-6746. Reports the biochemical characterization of purified DesII and the mechanistic implications for the overall C4 deoxygenation. The deoxygenation at the C4 position is proposed to proceed via an amino sugar intermediate. DesII is shown to be a member of the S-adenosylmethionine (SAM) family of radical enzymes. The involvement of a SAM radical in the reaction with DesII identifies a new strategy for deoxygenation reactions of sugars.
17. Nedal A., and Zotchev S.B. Biosynthesis of deoxyaminosugars in antibiotic-producing bacteria. Appl Microbiol Biotechnol 64 (2004) 7-15. In this mini-review, the proposed biosynthetic pathways for the deoxyaminosugar components of both macrolide and non-macrolide antibiotics are highlighted.
18. Zhao Z., Hong L., and Liu H.-w. Characterization of protein encoded by spnR from the spinosyn gene cluster of Saccharopolyspora spinosa: mechanistic implications for forosamine biosynthesis. J Am Chem Soc 127 (2005) 7692-7693
19. Melancon III C.E., Yu W.-l., and Liu H.-w. TDP-mycaminose biosynthetic pathway revised and conversion of desosamine pathway to mycaminose pathway with one gene. J Am Chem Soc 127 (2005) 12240-12241
20. Hofmann C., Boll R., Heitmann B., Hauser G., Duerr C., Frerich A., Weitnauer G., Glaser S.J., and Bechthold A. Genes encoding enzymes responsible for biosynthesis of L-lyxose and attachment of eurekanate during avilamycin biosynthesis. Chem Biol 12 (2005) 1137-1143
21. Bililign T., Shepard E.M., Ahlert J., and Thorson J.S. On the origin of deoxypentoses: evidence to support a glucose progenitor in the biosynthesis of calicheamicin. ChemBioChem 3 (2002) 1143-1146
22. Takahashi H., Liu Y.-n., Chen H., and Liu H.-w. Biosynthesis of TDP-L-mycarose: the specificity of a single enzyme governs the outcome of the pathway. J Am Chem Soc 127 (2005) 9340-9341
23. Borisova S.A., Zhao L., Melancon III C.E., Kao C.-L., and Liu H.-w. Characterization of the glycosyltransferase activity of DesVII: analysis of and implications for the biosynthesis of macrolide antibiotics. J Am Chem Soc 126 (2004) 6534-6535. The first report to describe in vitro activity of the glycosyltransferase responsible for the attachment of TDP-desosamine to two macrolactones, DesVII from S. venezuelae. DesVII was shown to require the additional protein component DesVIII for its activity; thus, this report stands as the first disclosure of a two-component glycosyltransferase system.
24. Hong J.S.J., Kim W.S., Lee S.K., Koh H.S., Park H.S., Park S.J., Kim Y.S., and Yoon Y.J. The role of a second protein (DesVIII) in glycosylation for the biosynthesis of hybrid macrolide antibiotics in Streptomyces venezuelae. J Microbiol Biotechnol 15 (2005) 640-645
25. Lu W., Leimkuhler C., Gatto G.J., Kruger R.G., Oberthur M., Kahne D., and Walsh C.T. AknT is an activating protein for the glycosyltransferase AknS in L-aminodeoxysugar transfer to the aglycone of aclacinomycin A. Chem Biol 12 (2005) 527-534
26. Melancon III C.E., Takahashi H., and Liu H.-w. Characterization of TylM3/TylM2 and MydC/MycB pairs required for efficient glycosyltransfer in macrolide antibiotic biosynthesis. J Am Chem Soc 126 (2004) 16726-16727
27. Yuan Y., Chung H.S., Leimkuhler C., Walsh C.T., Kahne D., and Walker S. In vitro reconstitution of EryCIII activity for the preparation of unnatural macrolides. J Am Chem Soc 127 (2005) 14128-14129
28. Minami A., Uchida R., Eguchi T., and Kakinuma K. Enzymatic approach to unnatural glycosides with diverse aglycon scaffolds using glycosyltransferase VinC. J Am Chem Soc 127 (2005) 6148-6149. A report of an unusually aglycon-indiscriminant glycosyltransferase (VinC) and its application toward constructing small glycoside libraries with diverse hydrophobic aglycon scaffolds. Structural elements of aglycon recognition by VinC were proposed from modeling studies and were supported by the successful glycosylation of a designed aglycon.
29. Yang M., Proctor M.R., Bolam D.N., Errey J.C., Field R.A., Gilbert H.J., and Davis B.G. 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 (2005) 9336-9337
30. Hoffmeister D., Weber M., Draeger G., Ichinose K., Duerr C., and Bechthold A. Rational saccharide extension by using the natural product glycosyltransferase LanGT4. ChemBioChem 5 (2004) 369-371
31. Luzhetskyy A., Fedoryshyn M., Duerr C., Taguchi T., Novikov V., and Bechthold A. Iteratively acting glycosyltransferases involved in the hexasaccharide biosynthesis of landomycin A. Chem Biol 12 (2005) 725-729. Reports detailed studies on the biosynthesis of the hexasaccharide side chain of landomycin A, produced by S. cyanogenus, that revealed the function of each glycosyltransferase gene within the biosynthetic gene cluster. This is the first description of glycosyltransferases (LanGT1 and LanGT4) involved in natural product biosynthesis that are working iteratively on a growing oligosaccharide chain.
32. Salas A.P., Zhu L., Sanchez C., Brana A.F., Rohr J., Mendez C., and Salas J.A. Deciphering the late steps in the biosynthesis of the anti-tumour indolocarbazole staurosporine: sugar donor substrate flexibility of the StaG glycosyltransferase. Mol Microbiol 58 (2005) 17-27. Staurosporine biosynthesis was reconstituted in vivo in the heterologous host S. albus. Attachment of the sugar to the two indole nitrogens of the indolocarbazole core was shown to be dependent on the combined action of glycosyltransferase StaG and P450 oxygenase StaN. The StaG glycosyltransferase and StaN displayed flexibility with respect to the sugar donor.
33. Durr C., Hoffmeister D., Wohlert S.-E., Ichinose K., Weber M., von Mulert U., Thorson J.S., and Bechthold A. The glycosyltransferase UrdGT2 catalyzes both C- and O-glycosidic sugar transfers. Angew Chem Int Ed Engl 43 (2004) 2962-2965. The authors demonstrate, for the first time, that the urdamycin C-glycosyltransferase (UrdGT2) displays the unusual ability to generate both C-C and C-O glycosidic bonds. The UrdGT2-catalyzed production of an O-glycoside lends support for one of the two postulated mechanisms for C-glycosylation of aromatic polyketides.
34. Bililign T., Hyun C.-G., Williams J.S., Czisny A.M., and Thorson J.S. The hedamycin locus implicates a novel aromatic PKS priming mechanism. Chem Biol 11 (2004) 959-969
35. Fischbach M.A., Lin H., Liu D.R., and Walsh C.T. In vitro characterization of IroB, a pathogen-associated C-glycosyltransferase. Proc Natl Acad Sci USA 102 (2005) 571-576
36. Fu X., Albermann C., Jiang J., Liao J., Zhang C., and Thorson J.S. Antibiotic optimization via in vitro glycorandomization. Nat Biotechnol 21 (2003) 1467-1469. Seminal report of the glycorandomization proof-of-concept. This study reports both the use of GtfE to construct monoglycosylated vancomycin variants and the downstream application of chemoselective ligation to produce analogs that rival vancomycin in potency.
37. Luzhetskyy A., Vente A., and Bechthold A. Glycosyltransferases involved in the biosynthesis of biologically active natural products that contain oligosaccharides. Mol Biosyst 1 (2005) 117-126
38. Minami A., Kakinuma K., and Eguchi T. Aglycon switch approach toward unnatural glycosides from natural glycoside with glycosyltransferase VinC. Tetrahedron Lett 46 (2005) 6187-6190. A new aglycon switch approach using glycosyltransferase VinC was explored to create unnatural glycosides from a natural glycoside in a one-pot reaction. This aglycon switch comprises from two reactions, where TDP-vicenisamine generated in situ from natural glycoside vicenistatin and TDP by the reverse reaction is transferred to the targeted additional aglycons to form unnatural vicenisaminides by the forward reaction. The intermediacy of TDP-vicenisamine in this study was postulated solely on the basis of high performance liquid chromatography.
39. Luzhetskyy A., Taguchi T., Fedoryshyn M., Duerr C., Wohlert S.-E., Novikov V., and Bechthold A. LanGT2 catalyzes the first glycosylation step during landomycin A biosynthesis. ChemBioChem 6 (2005) 1406-1410
40. Albermann C., Soriano A., Jiang J., Vollmer H., Biggins J.B., Barton W.A., Lesniak J., Nikolov D.B., and Thorson J.S. Substrate specificity of NovM: implications for novobiocin biosynthesis and glycorandomization. Org Lett 5 (2003) 933-936
41. Mulichak A.M., Lu W., Losey H.C., Walsh C.T., and Garavito R.M. Crystal structure of vancosaminyltransferase GtfD from the vancomycin biosynthetic pathway: interactions with acceptor and nucleotide ligands. Biochemistry 43 (2004) 5170-5180. Reports the X-ray crystal structure of the third and last unique glycosyltransferase from the vancomycin group series, GtfD. The structure was determined as a ternary complex with both TDP and the natural glycopeptide acceptor substrate. It was shown that the two domains of the protein were more interdependent in terms of substrate binding and overall structure than was evident from the structures of closely related glycosyltransferases GtfA and GtfB.
42. Solenberg P.J., Matsushima P., Stack D.R., Wilkie S.C., Thompson R.C., and Baltz R.H. Production of hybrid glycopeptide antibiotics in vitro and in Streptomyces toyocaensis. Chem Biol 4 (1997) 195-202
43. Madduri K., Kennedy J., Rivola G., Inventi-Solari A., Filippini S., Zanuso G., Colombo A.L., Gewain K.M., Occi J.L., MacNeil D.J., et al. Production of the antitumor drug epirubicin (4′-epidoxorubicin) and its precursor by a genetically engineered strain of Streptomyces peucetius. Nat Biotechnol 16 (1998) 69-74
44. Sanchez C., Zhu L., Brana A.F., Salas A.P., Rohr J., Mendez C., and Salas J.A. Combinatorial biosynthesis of antitumor indolocarbazole compounds. Proc Natl Acad Sci USA 102 (2005) 461-466. By co-expressing different combinations of genes from the rebbecamycin and staurosporine biosynthetic pathways, and a set of genes encoding uniquely regioselective halogenases, the authors achieved the production of >30 novel indolocarbazole compounds in an actinomycete host. An excellent example of contemporary pathway engineering.
45. Zhao L.S., Que N.L.S., Xue Y.Q., Sherman D.H., and Liu H.W. Mechanistic studies of desosamine biosynthesis: C-4 deoxygenation precedes C-3 transamination. J Am Chem Soc 120 (1998) 12159-12160
46. Hong J.S.J., Park S.H., Choi C.Y., Sohng J.K., and Yoon Y.J. New olivosyl derivatives of methymycin/pikromycin from an engineered strain of Streptomyces venezuelae. FEMS Microbiol Lett 238 (2004) 391-399
47. Lombo F., Gibson M., Greenwell L., Brana A.F., Rohr J., Salas J.A., and Mendez C. Engineering biosynthetic pathways for deoxysugars: branched-chain sugar pathways and derivatives from the antitumor tetracenomycin. Chem Biol 11 (2004) 1709-1718
48. Perez M., Lombo F., Zhu L., Gibson M., Brana A.F., Rohr J., Salas J.A., and Mendez C. Combining sugar biosynthesis genes for the generation of L- and D-amicetose and formation of two novel antitumor tetracenomycins. Chem Commun 36 (2005) 1604-1606
49. Ostash B., Rix U., Rix L.L.R., Liu T., Lombo F., Luzhetskyy A., Gromyko O., Wang C., Brana A.F., Mendez C., et al. Generation of new landomycins by combinatorial biosynthetic manipulation of the lndGT4 gene of the landomycin E cluster in S. globisporus. Chem Biol 11 (2004) 547-555
50. Pelzer S., Vente A., and Bechthold A. Novel natural compounds obtained by genome-based screening and genetic engineering. Curr Opin Drug Discov Devel 8 (2005) 228-238. Examples of recent advances in the application of new technologies, such as genetic engineering and screening, for the discovery and development of important novel drugs are discussed in this review.
51. Yang J., Fu X., Liao J., Liu L., and Thorson J.S. Structure-based engineering of E. coli galactokinase as a first step toward in vivo glycorandomization. Chem Biol 12 (2005) 657-664. This work reveals a homology model for further structure-based galactokinase engineering and highlights a prototype strain for in vivo phosphorylation of unnatural sugars. This notable success stands as the first step toward constructing short sugar-activation pathways in vivo and, ultimately, a universal glycorandomization strain for in vivo natural product glycodiversification.
52. Zhang C., Albermann C., Fu X., Peters N.R., Chisholm J.D., Zhang G., Gilbert E.J., Wang P.G., Van Vranken D.L., and Thorson J.S. RebG and RebM-catalyzed indolocarbazole diversification. ChemBioChem 7 (2006) 795-804