Mutasynthesis of glycopeptide antibiotics: variations of vancomycin's AB-ring amino acid 3,5-dihydroxyphenylglycine.
In the mutasynthetic approach, the DeltadpgA mutant of the vancomycin-type glycopeptide antibiotic producer Amycolatopsis balhimycina, which is deficient in the synthesis of 3,5-dihydroxyphenylglycine (DPg), was supplemented with synthetic DPg analogues to obtain the corresponding modified glycopeptides. Sterically more demanding 3,5-disubstituted methoxy derivatives as well as monosubstituted DPg analogues were accepted as substrates. These facts indicate that steric and electronic requirements suffice in several cases for the oxidative closure of the AB ring, thus leading to the generation of novel antibiotically active glycopeptide derivatives. The results represent a further step in evaluating the potential of mutasynthesis for peptidic secondary metabolites.
Weist
Stefan
S
Institute of Organic Chemistry, Auf der Morgenstelle 18, Germany.
Kittel
Claudia
C
Bischoff
Daniel
D
Bister
Bojan
B
Pfeifer
Volker
V
Nicholson
Graeme J
GJ
Wohlleben
Wolfgang
W
Süssmuth
Roderich D
RD
D039903:Actinobacteria / Q000235:genetics* / Q000378:metabolism*; D000900:Anti-Bacterial Agents / Q000096:biosynthesis* / Q000737:chemistry; D003470:Culture Media; D005998:Glycine / Q000031:analogs & derivatives* / Q000737:chemistry*; D006020:Glycopeptides / Q000096:biosynthesis* / Q000737:chemistry; D008968:Molecular Conformation; D009154:Mutation / Q000502:physiology*; D012118:Resorcinols / Q000737:chemistry*; D021241:Spectrometry, Mass, Electrospray Ionization; D014640:Vancomycin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry
D000900:Anti-Bacterial Agents; D003470:Culture Media; D006020:Glycopeptides; D012118:Resorcinols; C087127:balhimycin; C079215:3,5-dihydroxyphenylglycine; D014640:Vancomycin; D005998:Glycine