To develop a strategy for improved production of clavulanic acid (CA), we investigated the effect of using oils on cell growth and CA production during the fermentation of Streptomyces clavuligerus NRRL 3585. In this analysis, triolein, whose fatty acid is oleic acid only, was the best oil source for CA production, but free fatty acids generated from the hydrolysis of oils in a culture broth ne...

The claR of Streptomyces clavuligerus in the clavulanic acid gene cluster encodes a transcriptional regulator that controls clavulanic acid biosynthesis. The main goal of this study was isolation and molecular detection of the claR gene and its cloning in the Streptomyces specific vector (pMA:: hyg). By cinsideration of the claR gene’s start codon, the specific primers were designed. After geno...

The gene encoding BLIP, a beta-lactamase-inhibitory protein, was disrupted in wild-type Streptomyces clavuligerus and in a clavulanic acid non-producing mutant. The resulting BLIP mutant and BLIP/clavulanic acid double mutant showed no residual proteinaceous beta-lactamase-inhibitory activity, indicating that only a single beta-lactamase-inhibitory protein exists in S. clavuligerus. The lack of...

A regulatory gene (ccaR), located within the cephamycin gene cluster of Streptomyces clavuligerus, is linked to a gene (blp) encoding a protein similar to a beta-lactamase-inhibitory protein. Expression of ccaR is required for cephamycin and clavulanic acid biosynthesis in S. clavuligerus. The ccaR-encoded protein resembles the ActII-ORF4, RedD, AfsR, and DnrI regulatory proteins of other Strep...

The β-lactamase inhibitor, clavulanic acid is frequently used in combination with β-lactam antibiotics to treat a wide spectrum of infectious diseases. Clavulanic acid prevents drug resistance by pathogens against these β-lactam antibiotics by preventing the degradation of the β-lactam ring, thus ensuring eradication of these harmful microorganisms from the host. This systematic review provides...

Clavulanic acid (CA) is a powerful inhibitor of the beta-lactamases, enzymes produced by bacteria resistants to penicillin and cefalosporin. This molecule is produced industrially by strains of Streptomyces clavuligerus in complex media which carbon and nitrogen resources are supplied by inexpensive compounds still providing high productivity. The genetic production improvement using physical a...

the clar of streptomyces clavuligerus in the clavulanic acid gene cluster encodes a transcriptional regulator that controls clavulanic acid biosynthesis. the main goal of this study was isolation and molecular detection of the clar gene and its cloning in the streptomyces specific vector (pma:: hyg). by cinsideration of the clar gene’s start codon, the specific primers were designed. after geno...

In Streptomyces coelicolor bldA encodes the principal leucyl tRNA for translation of UUA codons and controls pigmented antibiotic production by the presence of TTA codons in the genes encoding the pathway-specific activators of actinorhodin and undecylprodigiosin biosynthesis. In Streptomyces clavuligerus the gene encoding the pathway-specific activator of both cephamycin C and clavulanic acid ...

A gene, pcbC, encoding the isopenicillin N synthase of Streptomyces griseus NRRL 3851, has been cloned in a 6.4-kb Bg/II DNA fragment and located in an internal 1.55-kb PvuII segment by hybridization with the Penicillium chrysogenum pcbC gene. Hybridization studies revealed the presence of homologous sequences in the DNAs of several Streptomyces strains and Nocardia lactamdurans. The S. griseus...

Streptomyces clavuligerus ATCC 27064 and S. clavuligerus ΔccaR::tsr cultures were grown in asparagine-starch medium, and samples were taken in the exponential and stationary growth phases. Transcriptomic analysis showed that the expression of 186 genes was altered in the ccaR-deleted mutant. These genes belong to the cephamycin C gene cluster, clavulanic acid gene cluster, clavams, holomycin, d...