| Tailoring of glycopeptide scaffolds by the acyltransferases from the teicoplanin and A-40,926 biosynthetic operons. | |
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MedLine Citation:
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PMID: 15664522 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The teicoplanin acyltransferase (Atf) responsible for N-acylation of the glucosamine moiety to create the teicoplanin lipoglycopeptide scaffold has recently been identified. Here we use that enzyme (tAtf) and the cognate acyltransferase from the related A-40,926 biosynthetic cluster (aAtf) to evaluate specificity for glycopeptide scaffolds and for the acyl-CoA donor. In addition to acylation of 2-aminoglucosyl glycopeptide scaffolds with k(cat) values of 400-2000 min(-1), both Atfs transfer acyl groups to regioisomeric 6-aminoglucosyl scaffolds and to glucosyl scaffolds at rates of 0.2-0.5 min(-1) to create variant lipoglycopeptides. Using the teicoplanin glycosyltransferase tGtfA, tAtf, and GtfD, a glycosyltransferase from the vancomycin producer, it is possible to assemble a novel lipoglycopeptide with GlcNAc at beta-OH-Tyr(6) and an N(6)-acyl-glucosaminyl-vancosamine at Phegly(4). This study illustrates the utility of chemo- and regioselective acyltransferases and glycosyltransferases to create novel lipoglycopeptides. |
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Authors:
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Ryan G Kruger; Wei Lu; Markus Oberthür; Junhua Tao; Daniel Kahne; Christopher T Walsh |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Chemistry & biology Volume: 12 ISSN: 1074-5521 ISO Abbreviation: Chem. Biol. Publication Date: 2005 Jan |
Date Detail:
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Created Date: 2005-01-24 Completed Date: 2005-08-11 Revised Date: 2007-11-14 |
Medline Journal Info:
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Nlm Unique ID: 9500160 Medline TA: Chem Biol Country: England |
Other Details:
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Languages: eng Pagination: 131-40 Citation Subset: IM |
Affiliation:
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Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Acyl Coenzyme A
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chemistry Acyltransferases / chemistry*, genetics, isolation & purification Anti-Bacterial Agents / chemistry* Cloning, Molecular Glycopeptides / chemical synthesis*, chemistry Hydrogen-Ion Concentration Kinetics Molecular Conformation Operon* Sensitivity and Specificity Stereoisomerism Teicoplanin / chemical synthesis, chemistry* Time Factors |
| Grant Support | |
ID/Acronym/Agency:
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GM 49338/GM/NIGMS NIH HHS; GM 66174/GM/NIGMS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/A 40926; 0/Acyl Coenzyme A; 0/Anti-Bacterial Agents; 0/Glycopeptides; 61036-62-2/Teicoplanin; EC 2.3.-/Acyltransferases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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