Tailoring of Glycopeptide Scaffolds by the Acyltransferases from the Teicoplanin and A-40,926 Biosynthetic Operons
2005; Elsevier BV; Volume: 12; Issue: 1 Linguagem: Inglês
10.1016/j.chembiol.2004.12.005
ISSN1879-1301
AutoresRyan G. Kruger, Wei Lü, Markus Oberthür, Junhua Tao, Daniel Kahne, Christopher T. Walsh,
Tópico(s)Glycosylation and Glycoproteins Research
ResumoThe 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 kcat 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 β-OH-Tyr6 and an N6-acyl-glucosaminyl-vancosamine at Phegly4. This study illustrates the utility of chemo- and regioselective acyltransferases and glycosyltransferases to create novel lipoglycopeptides.
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