The claR gene of Streptomyces clavuligerus, encoding a LysR-type regulatory protein controlling clavulanic acid biosynthesis, is linked to the clavulanate-9-aldehyde reductase (car) gene

Pérez‐Redondo, Rosario; Rodrı́guez-Garcı́a, Antonio; Martı́n, Juan F.; Liras, Paloma

doi:10.1016/s0378-1119(98)00106-1

Cited by 72 publications

(77 citation statements)

References 31 publications

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“…Growth and CA production by S. clavuligerus MA28 and MAG2 strains carrying claR expressed from ermE* and glpF promoters, respectively claR is pathway-specific regulatory gene in the CA biosynthesis cluster. Its overexpression increases CA biosynthesis, but this increase does not reach the levels obtained by ccaR overexpression in the wild-type S. clavuligerus (Pérez-Redondo et al, 1998). To investigate its effect on the CA yield of our industrial strain, we used ermE* and its own promoter (P claR ) to add its additional copy into the chromosome, as well as the glpF promoter for its multicopy expression in the cell.…”

Section: Resultsmentioning

confidence: 99%

“…Furthermore, dual expression of the ccaR and cas2 genes via chromosomal integration induced a 23.8-fold increase in CA yield (Hung et al, 2007). Amplification of ccaR or claR regulatory genes yielded 3-times higher CA level in the wild-type S. clavuligerus (Pérez-Llarena et al, 1997;Pérez-Redondo et al, 1998). Increased dosage of the pleiotropic regulator AdpA enhanced CA production by almost 2-fold (López-García et al, 2010).…”

Section: Discussionmentioning

confidence: 99%

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Genetic engineering of an industrial strain of Streptomyces clavuligerusfor further enhancement of clavulanic acid production

Kurt‐Kızıldoğan¹,

Jaccard²,

Mutlu³

et al. 2017

Turk J Biol

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An industrial clavulanic acid (CA) overproducer Streptomyces clavuligerus strain, namely DEPA, was engineered to further enhance its CA production. Single or multiple copies of ccaR, claR (pathway-specific activators), and cas2 (CA synthase) genes under the control of different promoters were introduced into this strain. CA titers of the resulting recombinants were analyzed by HPLC in a dynamic fashion and compared to the vector-only controls and a wild-type strain of S. clavuligerus while their growth was monitored throughout fermentation. The addition of an extra copy of ccaR, under control of its own promoter or constitutive ermE* promoter (P ermE* ), led to 7.6-and 2.3-fold increased volumetric levels of CA in respective recombinants, namely the AK9 and ID3 strains. Its highly stable multicopy expression by the glpF promoter (P glpF ) provided up to 25.9-fold enhanced volumetric CA titers in the respective recombinant, IDG3. claR expression controlled with its own promoter or ermE* and glpF-mediated amplification in an industrial strain brought about only about 1.2-fold increase in the volumetric CA titers. An extra copy of cas2 integration with P ermE* into the S. clavuligerus DEPA genome led to 3.8-fold higher volumetric CA production by GV61. Conclusively, multicopy expression of ccaR under P glpF can result in significantly improved industrial high-titer CA producers.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Genetic engineering of an industrial strain of Streptomyces clavuligerusfor further enhancement of clavulanic acid production

Kurt‐Kızıldoğan¹,

Jaccard²,

Mutlu³

et al. 2017

Turk J Biol

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“…2B [31]. The deduced protein product of Orf22 exhibits similarity to members of the EnvZ family of HK, including the H-box (His-283 being the putative phosphorylation site) and the N and G motifs [32,33] (Fig. 2A).…”

Section: Discussionmentioning

confidence: 97%

A Two-component Regulatory System Involved in Clavulanic Acid Production

Jnawali

Liou

et al. 2008

J Antibiot

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A pair of genes encoding the bacterial twocomponent regulatory system, orf22 and orf23, was found next to the clavulanic acid gene cluster of Streptomyces clavuligerus NRRL3585. Orf23 was deleted for the construction of S. clavuligerus/D orf23. Although growth and morphological analyses showed no differences between S. clavuligerus/D orf23 and wild-type, the production of clavulanic acid in S. clavuligerus/D orf23 was found to be decreased. In addition, the co-overexpression of orf22/orf23 in wild-type resulted in an enhanced 1.49-fold production of clavulanic acid, and the complementation of orf22/orf23 in S. clavuligerus/D orf23 restored clavulanic acid production about 80% as normal levels. These results demonstrate that the orf22/orf23 two-component regulatory system participates as a positive regulator of the biosynthesis of clavulanic acid and increased levels of orf22/orf23 can contribute to enhanced production of clavulanic acid in S. clavuligerus.

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“…The situation is reminiscent of the one found in the closest ThnI homologue, ClaR, which activates transcription of late clavulanic acid biosynthetic genes in S. clavuligerus. 17,18 ClaR is expressed as a monocistronic transcript from its own promoter, as well as co-transcribed with a biosyntheticregulated gene as a bicistronic transcript, where a similar read through of transcription spanning a stem-loop structure was observed. 17 …”

Section: Regulation Of Thienamycin Biosynthesis In Streptomyces Cattleyamentioning

confidence: 99%

Transcriptional organization of ThnI-regulated thienamycin biosynthetic genes in Streptomyces cattleya

et al. 2010

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The claR gene of Streptomyces clavuligerus, encoding a LysR-type regulatory protein controlling clavulanic acid biosynthesis, is linked to the clavulanate-9-aldehyde reductase (car) gene

Cited by 72 publications

References 31 publications

Genetic engineering of an industrial strain of Streptomyces clavuligerusfor further enhancement of clavulanic acid production

Genetic engineering of an industrial strain of Streptomyces clavuligerusfor further enhancement of clavulanic acid production

A Two-component Regulatory System Involved in Clavulanic Acid Production

Transcriptional organization of ThnI-regulated thienamycin biosynthetic genes in Streptomyces cattleya

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