Glycopeptides biosynthesis

The investigation of the glycopeptide biosynthesis has been a main focus of many research groups over the past 5 years, and currently, a relatively detailed picture already exists of the biosynthetic assembly. As a consequence, this topic has also been the subject of several review articles, which give an overview of the current status of research. ... 

Puk O, Huber P, Bischoff D, Recktenwald J, Jung G, Sussmuth RD, van Pee KH, Wohlleben W, Pelzer S. (2002) Glycopeptide biosynthesis in Amycolatopsis mediterranei DSM5908 function of a halogenase and a haloperoxidase/perhydrolase. Chem Biol 9 225-235... 

Glycopeptides Vancomycin Teicoplanin Reprogramming peptidoglycan biosynthesis... 

Pharmacology Vancomycin is a tricyclic glycopeptide antibiotic that inhibits cell-wall biosynthesis. It also alters bacterial-cell-membrane permeability and RNA synthesis. Pharmacokinetics ... 

The main function of the ester 34 in bacterial cells seems to be its participation in the biosynthesis of the glycopeptide cell-wall polymer. If this process is blocked, there results the accumulation of a high concentration of sugar nucleotide precursors in the cell. A number of these compounds have been isolated the simplest one is the ester of uridine 5 -pyrophosphate with N-acetylmuramic acid [2-acetamido-3-0-(D-l-carboxyethyl)-2-deoxy-D-glucose] (37), first obtained from Staphylococcus aureus cells that had been treated with penicillin7,151 or Gentian Violet.144 An intermediate in the biosynthesis of 37 was isolated and shown to be the 3 -enolpyruvate ether152,153 (38). 

Purification of some enzymes participating in the biosynthesis of glycopeptide cell-wall precursors has also been achieved. Examples include preparation of the enzymes necessary for synthesis of the enol ether 38 (see Section 11,6, p. 328),152-153-450 reduction of the enol ether to the muramic acid derivative,152-450,451 and the addition to the latter of amino acids452-456 or the dipeptide D-alanyl-D-alanine.160-457-458... 

Fig. 45.—Pathway of the Biosynthesis of Lipid-linked Oligosaccharide Precursor of the N-Acetyl-lactosaminic Type of Glycans, and of the Intermediary Glycopeptide. (See general reviews 126-136, 226, and 227.)...

Siissmuth RD, Pelzer S, Nicholson G, Walk T, Wohlleben W, Jung G (1999) New Advances in the Biosynthesis of Glycopeptide Antibiotics of the Vancomycin Type from Amycolatopsis mediterranei. Angew Chem Int Ed 38 1976... 

T. Kinoshita Enzymes required for biosynthesis of GPI-anchored proteins H. Kunz Synthetic glycopeptides for the development of antitumor vaccines M. A. J. Ferguson GPI and glycoprotein biosynthesis as targets for anti-parasite design... 

Sosio M, Stinchi S, Beltrametti F et al (2003) The gene cluster for the biosynthesis of the glycopeptide antibiotic A40926 by Nonomuraea species. Chem Biol 10 541-549... 

NE Allen, JN Hobbs Jr, TI Nicas. Inhibition of peptidoglycan biosynthesis in vancomycin-susceptible and -resistant bacteria by a semisynthetic glycopeptide antibiotic. Antimicrob Agents Chemother 40 2356-2362, 1996. 

Vancomycin, a natural product that was first approved in 1955, is still the prototype for structural variations with the same mechanism of action the binding to the terminal L-Lys-D-Ala-D-Ala tripeptide in Gram-positive cell wall biosynthesis. The compounds below are semi-synthetic modifications of the same basic structural class (glycopeptides) as the prototype vancomycin, thus following in the chemical footsteps of the (1-lactams currently, there are three semi-synthetic glycopeptides, oritavancin 39, telavancin 40 and dalba-vancin 41, in late stage clinical development. 

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