Deoxysugars in glycopeptide antibiotics: Enzymatic synthesis of TDP-l-epivancosamine in chloroeremomycin biosynthesis
AUTOR(ES)
Chen, Huawei
FONTE
The National Academy of Sciences
RESUMO
The 2,3,6-trideoxysugar l-epivancosamine is the terminal sugar added to the aglycone scaffold in chloroeremomycin, a member of the vancomycin family of glycopeptide antibiotics. Five proteins from the chloroeremomycin biosynthetic cluster, ORF14 and ORF23 to ORF26, have been expressed heterologously in Escherichia coli and purified to near homogeneity, and each has been characterized for an enzymatic activity. These five enzymes reconstitute the complete biosynthesis of TDP-l-epivancosamine from TDP-4-keto-6-deoxy-d-glucose. This process involves C-2 deoxygenation, C-3 amination and methylation, C-5 epimerization, and C-4 ketoreduction. Intermediates and the final product of this pathway have been identified by mass spectrometry and NMR. The pathway established here represents the complete in vitro reconstitution of an unusual sugar for an important class of antibiotics and sets the groundwork for future combinatorial biosynthesis for new bioactive compounds.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=17274Documentos Relacionados
- Hexapeptide Derivatives of Glycopeptide Antibiotics: Tools for Mechanism of Action Studies
- Structure of the TDP-epi-vancosaminyltransferase GtfA from the chloroeremomycin biosynthetic pathway
- Enzymatic Synthesis of Aminoglycoside Antibiotics: Novel Adenosylmethionine:2-Deoxystreptamine N-Methyltransferase Activities in Hygromycin B- and Spectinomycin-Producing Streptomyces spp. and Uses of the Methylated Products
- Enzymatic Modification of Aminoglycoside Antibiotics: a New 6′-N-Acetylating Enzyme from a Pseudomonas aeruginosa Isolate
- Enzymatic Modification of Aminoglycoside Antibiotics: a New 3-N-Acetylating Enzyme from a Pseudomonas aeruginosa Isolate