Rational Saccharide Extension by Using the Natural Product Glycosyltransferase LanGT4

Hoffmeister, Dirk; Weber, Mathias; Dräger, Gerald; Ichinose, Koji; Dürr, Clemens; Bechthold, Andreas

doi:10.1002/cbic.200300793

Cited by 20 publications

(12 citation statements)

References 13 publications

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“…[2,13] LanGT4 was shown to be a rhodinosyltransferase, exhibiting broad substrate specificity. [13,15] In this study we now report that LanGT3 is involved in the attachment of the fourth sugar of the hexasaccharide chain. In contrast to LanGT1 and LanGT4, this enzyme seems to be much more specific, as we were not able to synthesize novel urdamycin derivatives when expressing lanGT3 in different S. fradiae mutants.…”

Section: General Implicationsmentioning

confidence: 85%

Function of lanGT3, a Glycosyltransferase Gene Involved in Landomycin A Biosynthesis

et al. 2004

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The glycosyltransferase gene lanGT3, involved in the biosynthesis of the angucyclic antibiotic landomycin A, has been characterised by targeted gene deletion. A lanGT3 mutant was shown to produce landomycin E, which consists of a trisaccharide side chain attached to the polyketide moiety. Expression of lanGT3 in the mutant restored landomycin A production. Our results indicate that LanGT3 is responsible for the transfer of the fourth sugar during landomycin A biosynthesis.

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Section: General Implicationsmentioning

confidence: 85%

Function of lanGT3, a Glycosyltransferase Gene Involved in Landomycin A Biosynthesis

et al. 2004

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“…strain Tü 6368 seems to be an interesting candidate for studying the available glycosyl transferases in the light of their regio-, stereo-and substrate specifity. They may become valuable tools for genetically based combinatorial methods in the biosynthesis of biological active glycosides [18].…”

Section: Discussionmentioning

confidence: 99%

Retymicin, Galtamycin B, Saquayamycin Z and Ribofuranosyllumichrome, Novel Secondary Metabolites from Micromonospora sp. Tü 6368

et al. 2005

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A detailed screening of the secondary metabolite pattern from Micromonospora sp. strain Tü 6368 resulted in the isolation of ten compounds belonging to five different structural families. The structures of the novel compounds 1-(a -ribofuranosyl)-lumichrome (3), retymicin (7), galtamycin B (11) and saquayamycin Z (14) were assigned by spectroscopic methods and chemical transformations. This strain fits our hypothesis that the metabolite analysis of biosynthetically talented strains leads readily to novel compounds.

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“…One possible application is the conversion of anthralin and its 1,2-dihydroxy-derivative to the corresponding C-or Oglycosides to mitigate the inflammatory site effect of these potential antipsoriatica [201]. More examples for glycosyltransferases with some relaxed specificity towards "aglycone" substrates are LanGT1 [202], LanGT4 [202], NovM [123], enzyme variants of UrdGT1b/GT1c which were produced by mutation and gene-shuffling [24,203], OleG2 and OleG1 from the oleandomycin producer Streptomyces antibioticus [40], MtmGIII and MtmGIV from the mithramycin producer Streptomyces argillaceus [200], DesVII from the methymycin/pikromycin producer Streptomyces venezuelae [55,204], and EryCIII from the erythromycin producer Saccharopolyspora erythraea which is capable of transferring dTDP-D-desosamine (6) to 3-Orhamnosyl-erythronolide B [39,42,205].…”

Section: Expression Of Pathway Genes In Other Microbial Host Systemsmentioning

confidence: 98%

Nucleotide Deoxysugars: Essential Tools for the Glycosylation Engineering of Novel Bioactive Compounds

Rupprath¹,

Schumacher²,

Elling

2005

CMC

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The irreversible spread of new resistance mechanisms against existing therapeutical antibiotics has led to the development of technologies and strategies for the glycosylation engineering of novel antibiotics. Amino-, C-branched and O-methylated 6-deoxyhexoses play a favourite role in the biosynthesis of clinically important antibiotics like tylosin, erythromycin or oleandomycin and are essential for the antibiotic activity. They are transferred onto the aglycon by glycosyltransferases using dTDP-activated deoxyhexoses. The in vitro biochemical characterization of the biosynthetic enzymes and the glycosyltransferases are, however, hampered due to the poor synthetic access to dTDP-activated deoxysugars and their biosynthetic intermediates. The overcoming of the poor availability of dTDP-activated sugars was the target of several researchers to fulfil their distinct aims with these sugars which were mostly involved in the synthesis of different biological active compounds. Several completely different strategies were used in the past years to improve the availability of dTDP-activated deoxysugars, varying from complete enzymatic synthesis via syntheses using reaction technology for yield optimization to full organic synthesis or shortcuts like the decomposition of commercially available antibiotics and later chemical activation of the sugar moieties. This review gives a survey of the synthesis of dTDP-activated sugars by chemical and chemoenzymatic approaches and discusses the promiscuity of glycosyltransferases to evaluate the chances for applying them for the production of new bioactive compounds. It summarizes the most important enzymes in the field of synthesis using biosynthetic pathway enzymes and describes solutions for occurring challenges during application. Finally, this review will give a survey about the availability of dTDP-activated sugars in sufficient scale and will also point at important sugars which are still bottlenecks and difficult to synthesize and therefore should become a target for enhanced research efforts.

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Rational Saccharide Extension by Using the Natural Product Glycosyltransferase LanGT4

Cited by 20 publications

References 13 publications

Function of lanGT3, a Glycosyltransferase Gene Involved in Landomycin A Biosynthesis

Function of lanGT3, a Glycosyltransferase Gene Involved in Landomycin A Biosynthesis

Retymicin, Galtamycin B, Saquayamycin Z and Ribofuranosyllumichrome, Novel Secondary Metabolites from Micromonospora sp. Tü 6368

Nucleotide Deoxysugars: Essential Tools for the Glycosylation Engineering of Novel Bioactive Compounds

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