Pérez-Llarena F, Martín J F, Galleni M, Coque J J, Fuente J L, Frère J M, Liras P
Faculty of Biology, Department of Ecology, Genetics and Microbiology, University of Léon, Spain.
J Bacteriol. 1997 Oct;179(19):6035-40. doi: 10.1128/jb.179.19.6035-6040.1997.
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.
编码β-内酰胺酶的基因(bla)存在于棒状链霉菌的头孢霉素基因簇中,该菌株可产生克拉维酸和一种β-内酰胺酶抑制蛋白。bla基因位于编码去乙酰氧头孢菌素C合酶的cefE下游5.1 kb处,且方向相反。bla基因编码一种由332个残基组成的蛋白质(Mr,35218),与放线菌产生的其他A类β-内酰胺酶相似。A类β-内酰胺酶的SDN保守基序以及分子中其他保守区域的氨基酸发生修饰(变为SDG),可能解释了该蛋白质青霉素酶和头孢菌素酶活性较低的原因。该β-内酰胺酶已被纯化至同质,并发现它能结合[3H]苄青霉素,这一结果反映了一个限速脱酰步骤。在所有测试的头孢霉素产生菌中都发现了与bla同源的核苷酸序列,但其他几种产生β-内酰胺酶的链霉菌物种并不包含β-内酰胺抗生素生物合成的基因。