Manipulation of the physiology of clavulanic acid production in Streptomyces clavuligerus

Ives, Paul R.; Bushell, Michael E.

doi:10.1099/00221287-143-11-3573

Cited by 44 publications

(25 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In Streptomyces, ammonium has been reported to be an inhibitory substrate for growth, especially when supplied in high concentrations (Ives & Bushell, 1997). This could explain the lag phase observed in the medium with ammonium.…”

Section: Utilization Of Carbon and Nitrogen Sources For Growthmentioning

confidence: 69%

Nitrogen source governs the patterns of growth and pristinamycin production in ‘Streptomyces pristinaespiralis’

Voelker¹,

Altaba²

2001

Microbiology

View full text Add to dashboard Cite

Phosphate-limited synthetic culture media were designed to investigate the growth and the pristinamycin production of ' Streptomyces pristinaespiralis ' using different nitrogen sources. During balanced growth, either mineral or organic nitrogen sources were readily utilized. However, glutamate and alanine were used as both nitrogen and carbon source, sparing the utilization of the primary carbon source, glucose. Valine was utilized only for its nitrogen and consequently 2-ketoisovalerate was excreted in the medium. Ammonium prevented the utilization of nitrate. Upon phosphate limitation, glycerol, originating from the breakdown of teichoic acids, was released, allowing the recovery of phosphate from the cell wall and the continuation of growth. Under such conditions, ammonium was excreted following the consumption of glutamate and alanine and was later reassimilated after exhaustion of the primary nitrogen source. The mode of utilization of valine prevented the production of pristinamycins due to excretion of 2-ketoisovalerate, one of their direct precursors. For other nitrogen sources, pristinamycin production was controlled by nitrogen catabolic regulation linked to the residual level of ammonium. In the case of nitrate, the negative regulation was alleviated by the absence of ammonium and production then occurred precociously. In the case of amino acids and ammonium, production was delayed until after exhaustion of amino acids and depletion of ammonium.

show abstract

Section: Utilization Of Carbon and Nitrogen Sources For Growthmentioning

confidence: 69%

Nitrogen source governs the patterns of growth and pristinamycin production in ‘Streptomyces pristinaespiralis’

Voelker¹,

Altaba²

2001

Microbiology

View full text Add to dashboard Cite

show abstract

“…The possible reasons for the observed results can be explained with respect to the biosynthetic pathway for clavulanic acid production. It is well documented that pyruvate acts as C3 precursor, whereas arginine acts as the C5 precursor for clavulanic acid production (17). Radiolabeled feeding experiments have indicated arginine and ornithine to be efficiently incorporated into clavulanic acid structure (18,19).…”

Section: Effect Of Phmentioning

confidence: 99%

A statistical approach using L25 orthogonal array method to study fermentative production of clavulanic acid by Streptomyces clavuligerus MTCC 1142

Saudagar

2007

Appl Biochem Biotechnol

View full text Add to dashboard Cite

Clavulanic acid is a naturally occurring antibiotic produced by Streptomyces clavuligerus. The present work reports on clavulanic acid production by Streptomyces clavuligerus MTCC 1142 using one-factor-at-a-time and L(25) orthogonal array. The one-factor-at-a-time method was adopted to investigate the effect of media components (i.e., carbon source, nitrogen source and inoculum concentration) and environmental factors such as pH for clavulanic acid production. Production of clavulanic acid by Streptomyces clavuligerus was investigated using seven different carbon sources (viz. glucose, sucrose, modified starch, rice-bran oil, soybean oil, palm oil, and glycerol) and six different nitrogen sources (viz. peptone, yeast extract, ammonium chloride, ammonium carbonate, sodium nitrate and potassium nitrate). A maximum yield of 140 microg/mL clavulanic acid was obtained in the medium containing soybean oil as a carbon source and yeast extract as nitrogen source. Subsequently, the concentration of soybean flour, soybean oil, dextrin, yeast extract and K2HPO4 were optimized using L25 orthogonal array method. The final optimized medium produced 500 microg/mL clavulanic acid at the end of 96 h as compared to 140 microg/mL before optimization. Synthesis of precursor molecules as a metabolic driving force is of considerable importance in antibiotic synthesis. Attempts to increase the clavulanic acid synthesis by manipulating the anaplerotic flux on C(3) and C(5) precursors by supplementing the medium with arginine, ornithine, proline, valine, leucine, isoleucine, pyruvic acid and alpha-ketoglutarate were successful. Supplementing the optimized medium with 0.1 M arginine and 0.1 M leucine increased the yield of clavulanic acid further to 1100 microg/mL and 1384 microg/mL respectively.

show abstract

“…In culture B2, a residual concentration of reducing sugars of approximately 2.2 g.L -1 was observed. S. clavuligerus is able to consume oligosaccharides; however, it is unable to assimilate glucose, which accumulated in the fermentation broth at the end of the cultivation (Ives and Bushell, 1997). In culture B1 (glycerol), the maximum concentrations (Cp max ) of CA and CephC (348.5 and 418.5 mg.L ) were reached after 54 and 72 h, respectively.…”

Section: Batch Culturesmentioning

confidence: 99%

Production of clavulanic acid and cephamycin C by Streptomyces clavuligerus under different fed-batch conditions

Bellão

Antonio

Araujo

et al. 2013

Braz. J. Chem. Eng.

View full text Add to dashboard Cite

-The effect of carbon source and feeding conditions on the production of clavulanic acid (CA) and cephamycin C (CephC) by Streptomyces clavuligerus was investigated. In fed-batch experiments performed with glycerol feeding, production of CA exceeded that of CephC, and reached 1022 mg.L ) was obtained in fed-batch cultivation with glycerol feeding. In fed-batch experiments performed with starch feeding, the production of CephC was in general higher than that of CA. A dissociation index (DI) was used to identify feeding conditions that favored production of CephC relative to CA. In all cultures with glycerol, DI values were less than unity, indicating higher production of CA compared to CephC. Conversely, in cultures fed with starch, the DI values obtained were greater than unity. However, no carbon source or feeding condition was able to completely dissociate the production of CA from that of CephC.

show abstract

Manipulation of the physiology of clavulanic acid production in Streptomyces clavuligerus

Cited by 44 publications

References 23 publications

Nitrogen source governs the patterns of growth and pristinamycin production in ‘Streptomyces pristinaespiralis’

Nitrogen source governs the patterns of growth and pristinamycin production in ‘Streptomyces pristinaespiralis’

A statistical approach using L25 orthogonal array method to study fermentative production of clavulanic acid by Streptomyces clavuligerus MTCC 1142

Production of clavulanic acid and cephamycin C by Streptomyces clavuligerus under different fed-batch conditions

Contact Info

Product

Resources

About