An erythromycin derivative produced by targeted gene disruption in Saccharopolyspora erythraea.
Derivatives of erythromycin with modifications at their C-6 position are generally sought for their increased stability at acid pH, which in turn may confer improved pharmacological properties. A recombinant mutant of the erythromycin-producing bacterium, Saccharopolyspora erythraea, produced an erythromycin derivative, 6-deoxyerythromycin A, that could not be obtained readily by chemical synthesis. This product resulted from targeted disruption of the gene, designated eryF (systematic nomenclature, CYP107), that apparently codes for the cytochrome P450, 6-deoxyerythronolide B (DEB) hydroxylase, which converts DEB to erythronolide B (EB). Enzymes normally acting on EB can process the alternative substrate DEB to form the biologically active erythromycin derivative lacking the C-6 hydroxyl group.
Weber
J M
JM
BioProcess Development, Department 451/R5, Abbott Laboratories, North Chicago, IL 60064.
Leung
J O
JO
Swanson
S J
SJ
Idler
K B
KB
McAlpine
J B
JB
D000595:Amino Acid Sequence; D001419:Bacteria / Q000235:genetics; D001426:Bacterial Proteins; D001483:Base Sequence; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D004252:DNA Mutational Analysis; D004269:DNA, Bacterial / Q000235:genetics; D004917:Erythromycin / Q000031:analogs & derivatives / Q000096:biosynthesis*; D005798:Genes, Bacterial; D006899:Mixed Function Oxygenases / Q000235:genetics*; D008969:Molecular Sequence Data; D010957:Plasmids; D015183:Restriction Mapping
D001426:Bacterial Proteins; D004269:DNA, Bacterial; D004917:Erythromycin; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; C054444:eryF protein, Saccharopolyspora erythraea