Glycopeptide antibiotic biosynthesis.
Glycopeptides such as vancomycin, teicoplanin and telavancin are essential for treating infections caused by Gram-positive bacteria. Unfortunately, the dwindled pipeline of new antibiotics into the market and the emergence of glycopeptide-resistant enterococci and other resistant bacteria are increasingly making effective antibiotic treatment difficult. We have now learned a great deal about how bacteria produce antibiotics. This information can be exploited to develop the next generation of antimicrobials. The biosynthesis of glycopeptides via nonribosomal peptide assembly and unusual amino acid synthesis, crosslinking and tailoring enzymes gives rise to intricate chemical structures that target the bacterial cell wall. This review seeks to describe recent advances in our understanding of both biosynthesis and resistance of these important antibiotics.
MG DeGroote Institute for Infectious Disease Research, Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada.
Grace
G
Yim
MG DeGroote Institute for Infectious Disease Research, Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada.
Maulik N
MN
Thaker
MG DeGroote Institute for Infectious Disease Research, Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada.
Kalinka
K
Koteva
MG DeGroote Institute for Infectious Disease Research, Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada.
Gerard
G
Wright
D000900:Anti-Bacterial Agents / Q000096:biosynthesis* / Q000494:pharmacology; D002473:Cell Wall / Q000378:metabolism; D015195:Drug Design; D024881:Drug Resistance, Bacterial; D006020:Glycopeptides / Q000096:biosynthesis* / Q000494:pharmacology; D006094:Gram-Positive Bacteria / Q000187:drug effects; D016908:Gram-Positive Bacterial Infections / Q000188:drug therapy / Q000382:microbiology; D006801:Humans; D058990:Molecular Targeted Therapy
D000900:Anti-Bacterial Agents; D006020:Glycopeptides