Utilization of ornithine and arginine as specific precursors of clavulanic acid

Romero‐García, Jorge; Liras, Paloma; Martı́n, Juan F.

doi:10.1128/aem.52.4.892-897.1986

Cited by 68 publications

(31 citation statements)

References 19 publications

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“…Indeed, ammonium interfered with arginine utilization, and at least two enzymes involved in the catabolism of this amino acid are regulatory targets. Arginase activity has been reported in S. clavuligerus and found to be induced by arginine (Romero et al, 1986). Our results confirmed this observation and also indicated that nitrogen control participates in arginase regulation, as described in other micro-organisms (Baumberg & Harwood, 1979;Broman et al, 1978).…”

Section: Bascaran C H a R D I S S O N A N D A F B R A~asupporting

confidence: 92%

Regulation of Nitrogen Catabolic Enzymes in Streptomyces clavuligems

Bascaráan¹,

Hardisson²,

Braña³

1989

Microbiology

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The levels of several enzymes involved in assimilation of different nitrogen compounds were investigated in Streptomyces clavuligerus in relation to the nitrogen source supplied to the cultures. Threonine dehydratase, serine dehydratase, proline dehydrogenase, histidase and urocanase were not decreased in the presence of ammonium. The latter two enzymes were induced by histidine in the culture medium, while proline dehydrogenase was induced by proline. Glutamine synthetase, urease and ornithine aminotransferase levels were higher with poor nitrogen sources and were repressed by ammonium. Arginase was induced by arginine and repressed by ammonium. Glutamine synthetase was rapidly inactivated upon addition of ammonium to the culture, and could be reactivated in vitro by treatment with snake venom phosphodiesterase, which suggested that adenylylation is involved in the inactivation. Three previously isolated mutants with abnormal glutamine synthetase activities showed pleiotropic effects on urease formation. All these data point to a mechanism controlling preferential utilization of some nitrogen sources in this species.

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Section: Bascaran C H a R D I S S O N A N D A F B R A~asupporting

confidence: 92%

Regulation of Nitrogen Catabolic Enzymes in Streptomyces clavuligems

Bascaráan¹,

Hardisson²,

Braña³

1989

Microbiology

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“…A 93.5% match was obtained, which indicates that the S. clavuligerus model predicts the activity of the diverse pathways for catabolism of the different carbon and nitrogen sources. These results are in good agreement with experimental reports [29][30][31].…”

Section: In Silico Prediction Of Carbon and Nitrogen Utilizationsupporting

confidence: 93%

An enhanced genome-scale metabolic reconstruction of Streptomyces clavuligerus identifies novel strain improvement strategies

Toro

Pinilla

Avignone–Rossa

et al. 2018

Bioprocess Biosyst Eng

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In this work, we expanded and updated a genome-scale metabolic model of Streptomyces clavuligerus. The model includes 1021 genes and 1494 biochemical reactions; genome-reaction information was curated and new features related to clavam metabolism and to the biomass synthesis equation were incorporated. The model was validated using experimental data from the literature and simulations were performed to predict cellular growth and clavulanic acid biosynthesis. Flux balance analysis (FBA) showed that limiting concentrations of phosphate and an excess of ammonia accumulation are unfavorable for growth and clavulanic acid biosynthesis. The evaluation of different objective functions for FBA showed that maximization of ATP yields the best predictions for cellular behavior in continuous cultures, while the maximization of growth rate provides better predictions for batch cultures. Through gene essentiality analysis, 130 essential genes were found using a limited in silico media, while 100 essential genes were identified in amino acid-supplemented media. Finally, a strain design was carried out to identify candidate genes to be overexpressed or knocked out so as to maximize antibiotic biosynthesis. Interestingly, potential metabolic engineering targets, identified in this study, have not been tested experimentally.

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“…S. clavuligerus produces several ,-lactam antibiotics, including clavulanic acid, a potent 1-lactamase inhibitor, and cephamycin C (13,24). Many studies have been carried out on the biosynthesis of cephamycins (2,8,26) and clavulanic acid (26,27) and the control of antibiotic biosynthesis by this strain, which is becoming a model microorganism for the study of cephamycin biosynthesis. The development of recombinant DNA technology in S. clavuligerus is of great interest but has been hampered by the difficulty in regenerating cells from protoplasts and by the unavailability of suitable cloning vectors and transformation systems.…”

mentioning

confidence: 99%

Efficient plasmid transformation of the beta-lactam producer Streptomyces clavuligerus

Garcia-Dominguez¹,

Martı́n²,

Mahro³

et al. 1987

Appl Environ Microbiol

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The conditions for optimal formation and regeneration of protoplasts of Streptomyces clavuligerus were established. The optimal temperature for regeneration of protoplasts and for transformation was 26 degrees C in three different regeneration media. The best efficiency of transformation was obtained with 40% polyethylene glycol 1000. The efficiencies of regeneration and transformation increased greatly when protoplasts were obtained from cultures in the early stationary phase of growth. The number of transformants per assay increased linearly with rising concentrations of protoplasts. However, the number of transformants per protoplast decreased at concentrations of protoplasts above 1.5 X 10(9). The total number of transformants rose linearly at increasing plasmid DNA concentrations, but the number of the transformants per microgram of DNA became constant at concentrations above 1 microgram of DNA. Transformation frequencies as high as 5 X 10(5) transformants per microgram of DNA were obtained when plasmid pIJ702 was isolated from S. clavuligerus but not when isolated from Streptomyces lividans.

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Utilization of ornithine and arginine as specific precursors of clavulanic acid

Cited by 68 publications

References 19 publications

Regulation of Nitrogen Catabolic Enzymes in Streptomyces clavuligems

Regulation of Nitrogen Catabolic Enzymes in Streptomyces clavuligems

An enhanced genome-scale metabolic reconstruction of Streptomyces clavuligerus identifies novel strain improvement strategies

Efficient plasmid transformation of the beta-lactam producer Streptomyces clavuligerus

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