Improvement of clavulanic acid production in Streptomyces clavuligerus F613-1 by using a claR - neo reporter strategy

Qin, Ronghuo; Zhong, Chunlong; Zong, Guanghua; Fu, Jiafang; Pang, Xiuhua; Cao, Guangxiang

doi:10.1016/j.ejbt.2017.05.002

Cited by 16 publications

(22 citation statements)

References 28 publications

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“…Several studies focused on the effect of nutrient concentrations and environmental cultivation conditions on CA biosynthesis, as Ser et al [7] reviewed. Additionally, genetic engineering tools have been applied to S. clavuligerus aimed to improve the cellular metabolic capabilities for CA production in submerged cultures [8][9][10].…”

Section: Introductionmentioning

confidence: 99%

Characterization of the Metabolic Response of Streptomyces clavuligerus to Shear Stress in Stirred Tanks and Single-Use 2D Rocking Motion Bioreactors for Clavulanic Acid Production

et al. 2019

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Streptomyces clavuligerus is a gram-positive filamentous bacterium notable for producing clavulanic acid (CA), an inhibitor of β-lactamase enzymes, which confers resistance to bacteria against several antibiotics. Here we present a comparative analysis of the morphological and metabolic response of S. clavuligerus linked to the CA production under low and high shear stress conditions in a 2D rocking-motion single-use bioreactor (CELL-tainer ®) and stirred tank bioreactor (STR), respectively. The CELL-tainer® guarantees high turbulence and enhanced volumetric mass transfer at low shear stress, which (in contrast to bubble columns) allows the investigation of the impact of shear stress without oxygen limitation. The results indicate that high shear forces do not compromise the viability of S. clavuligerus cells; even higher specific growth rate, biomass, and specific CA production rate were observed in the STR. Under low shear forces in the CELL-tainer® the mycelial diameter increased considerably (average diameter 2.27 in CELL-tainer® vs. 1.44 µm in STR). This suggests that CA production may be affected by a lower surface-to-volume ratio which would lead to lower diffusion and transport of nutrients, oxygen, and product. The present study shows that there is a strong correlation between macromorphology and CA production, which should be an important aspect to consider in industrial production of CA.

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Section: Introductionmentioning

confidence: 99%

Characterization of the Metabolic Response of Streptomyces clavuligerus to Shear Stress in Stirred Tanks and Single-Use 2D Rocking Motion Bioreactors for Clavulanic Acid Production

et al. 2019

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“…Studies investigating biosynthetic ways and genes correlated with the production of CA and other clavams have been performed [ 63 , 64 , 65 ]. CA biosynthesis involves early and late stages including oxidative reactions catalyzed by 2-oxoglutarate dependent dioxygenases.…”

Section: Producers Of β-Lactamases Inhibitorsmentioning

confidence: 99%

Production of β-Lactamase Inhibitors by Streptomyces Species

et al. 2018

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β-Lactamase inhibitors have emerged as an effective alternative to reduce the effects of resistance against β-lactam antibiotics. The Streptomyces genus is known for being an exceptional natural source of antimicrobials and β-lactamase inhibitors such as clavulanic acid, which is largely applied in clinical practice. To protect against the increasing prevalence of multidrug-resistant bacterial strains, new antibiotics and β-lactamase inhibitors need to be discovered and developed. This review will cover an update about the main β-lactamase inhibitors producers belonging to the Streptomyces genus; advanced methods, such as genetic and metabolic engineering, to enhance inhibitor production compared with wild-type strains; and fermentation and purification processes. Moreover, clinical practice and commercial issues are discussed. The commitment of companies and governments to develop innovative strategies and methods to improve the access to new, efficient, and potentially cost-effective microbial products to combat the antimicrobial resistance is also highlighted.

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“…Only a few strains of Streptomyces show sensitivity to UV radiation due to the absence of a repair process known as photo reactivation. However, it is worth mentioning that UV radiation has been successfully applied for mutagenesis of S. clavuligerus and S. coelicolor since these species have proved sensitive to such type of radiation [12,13,14]. Therefore, the objective of this work was to improve the CA production process in a submerged culture by selecting UV radiation mutants of the wild strain S. clavuligerus ATCC 27064.…”

Section: Introductionmentioning

confidence: 99%

Exploring the Optimization of UV Mutants of Streptomyces clavuligerus for Clavulanic Acid Production

Cruz-Hernández¹,

Vasconcelos²,

Teodoro³

et al. 2019

MRJI

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Streptomyces clavuligerus, initially described as a Cephamycin C producer, has been currently utilized to produce clavulanic acid (CA) which shows low antibiotic activity, being, however, a strong β-lactamase inhibitor, enzymes responsible for bacterial resistance to β-lactam antibiotics. Genetic improvement by physical and chemical agents is mandatory since, due to its genetic instability, industrial strains lose production capability making necessary a steady and frequent strain improvement and a screening procedure. The objective of this work was to obtain an increase in CA production in submerged cultures by utilizing mutants obtained by UV radiation of Original Research Articlewith this mutant, although a lower specific growth rate had been observed.

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Improvement of clavulanic acid production in Streptomyces clavuligerus F613-1 by using a claR - neo reporter strategy

Cited by 16 publications

References 28 publications

Characterization of the Metabolic Response of Streptomyces clavuligerus to Shear Stress in Stirred Tanks and Single-Use 2D Rocking Motion Bioreactors for Clavulanic Acid Production

Characterization of the Metabolic Response of Streptomyces clavuligerus to Shear Stress in Stirred Tanks and Single-Use 2D Rocking Motion Bioreactors for Clavulanic Acid Production

Production of β-Lactamase Inhibitors by Streptomyces Species

Exploring the Optimization of UV Mutants of Streptomyces clavuligerus for Clavulanic Acid Production

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