The bla gene of the cephamycin cluster of Streptomyces clavuligerus encodes a class A beta-lactamase of low enzymatic activity.
A gene (bla) encoding a beta-lactamase is present in the cephamycin gene cluster of Streptomyces clavuligerus, the strain producing clavulanic acid and a beta-lactamase inhibitory protein. The bla gene is located 5.1 kb downstream from and in the opposite orientation to cefE, encoding the deacetoxycephalosporin C synthase. The bla gene encodes a 332-residue protein (Mr, 35,218), similar to other class A beta-lactamases produced by actinomycetes. Modification (to SDG) of the SDN conserved motif of class A beta-lactamases as well as of amino acids in otherwise conserved regions in the molecule may explain the low penicillinase and cephalosporinase activities of the protein. The beta-lactamase has been purified to homogeneity and found to bind [3H]benzylpenicillin, a result reflecting a rate-limiting deacylation step. Nucleotide sequences homologous to bla were found in all tested cephamycin producers, but several other Streptomyces species which produce a beta-lactamase do not contain genes for beta-lactam antibiotic biosynthesis.
Pérez-Llarena
F
F
Faculty of Biology, Department of Ecology, Genetics and Microbiology, University of Léon, Spain.
Martín
J F
JF
Galleni
M
M
Coque
J J
JJ
Fuente
J L
JL
Frère
J M
JM
Liras
P
P
D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000096:biosynthesis / Q000378:metabolism; D001483:Base Sequence; D002513:Cephamycins / Q000096:biosynthesis*; D003001:Cloning, Molecular; D005798:Genes, Bacterial; D007700:Kinetics; D008969:Molecular Sequence Data; D008970:Molecular Weight; D010400:Penicillin G / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D013302:Streptomyces / Q000201:enzymology / Q000235:genetics*; D014170:Transformation, Genetic; D001618:beta-Lactamases / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism
D000900:Anti-Bacterial Agents; D002513:Cephamycins; D011994:Recombinant Proteins; D001618:beta-Lactamases; D010400:Penicillin G