1887

Abstract

The gene encoding BLIP, a eta-actamase-nhibitory rotein, was disrupted in wild-type and in a clavulanic acid non-producing mutant. The resulting BLIP mutant and BLIP/clavulanic acid double mutant showed no residual proteinaceous β-lactamase-inhibitory activity, indicating that only a single β-lactamase-inhibitory protein exists in . The lack of any proteinaceous β-lactamase-inhibitory activity in the and / mutants also indicates that BLP, the BLIP-like protein, encoded by does not possess β-lactamase-inhibitory activity despite its similarity to BLIP. The mutant and the / double mutant did not show any aberrant growth morphology, sporulation defects, or alterations in cephamycin C production or penicillin G resistance when compared to wild-type or to the single mutant. Mutants bearing the gene disruption did show an elevated level of production of clavam-2-carboxylate and hydroxymethyl clavam as well as clavulanic acid. This phenomenon was observed in the middle stages of production of these clavams but was not detected during maximum production. The production of BLIP was also determined to be down-regulated in a mutant, lacking the pathway-specific transcriptional regulator required for production of cephamycin C and clavulanic acid. Sequencing of the regions flanking the gene showed the presence of a partial open reading frame that encodes a DNA-binding protein, and several open reading frames apparently involved in the production of an ABC transporter.

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2001-02-01
2021-10-23
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