Enhancement of clavulanic acid production by Streptomyces sp MU-NRC77 via mutation and medium optimization

SAID, ISMAIL; Abdelwahed, Nayera A. M.; Awad, Hassan M.; Shallan, Madgy A.; El-Shahed, K. Y. I.; Abdel-Rahim, Emam A.

doi:10.4314/tjpr.v16i1.5

Cited by 8 publications

(4 citation statements)

References 21 publications

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“…Korbekandi et al 9 reported that the concentration of CA was increased 1.8 times after UV mutagenesis. In another study, Said et al 19 show that relatively safe mutagens like UV represent a very convenient system to enhance strains through random mutation. On the other hand, only a small number of researchers have utilized UV irradiation to overproduce CA.…”

Section: Resultsmentioning

confidence: 99%

Enhancement of clavulanic acid production by mutant Streptomyces clavuligerus

Vasconcelos¹

2018

JBMOA

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Background: Clavulanic acid (CA) is a potent β-lactamase inhibitor used to combat resistance to penicillin and cephalosporin antibiotics. There are several pathogenic microorganisms that are capable of secreting β-Lactamases. These enzymes catalyze the hydrolysis of the β-lactam ring of penicillins and cephalosporins, and their hydrolysis products have no antibiotic activity. Since the first clinical applications, the efficiency of the β-lactam antibiotics has been declining, due to the astonishing increasing number of bacteria capable of displaying β-lactam resistance. Thus, the genetic production improvement using physical and chemical mutagenic agents is an important strategy in programs of industrial production of bioactive metabolites, such as CA. Objective: The objective of the study was to enhance CA production using chemical and UV mutagenesis on Streptomyces clavuligerus. Methods: Streptomyces clavuligerus ATCC 27064 was used as the standard strain in all the experiments. The mutant strain was first obtained by chemical mutagenesis using the agent MMS and next the same strain undergoing one more mutation was obtained by UV light. Cellular biomass was analyzed based on the dry weight method and the concentration of CA was determined by HPLC analysis. Results: CA production increased by 28% with mutant strain when compared to the wild-type strain. The mutant strain obtained 812mg L-1 concentration in 72h of fermentation, while the wild-type strain obtained only 639.7.1mg L-1 at the same time, and the productivity at this moment was 11.28 and 8.88mg L-1 h-1 respectively. The mutant strain had a significant increase in biomass growth between 36 and 60h. Conclusion: The study showed that random mutations can lead to the improvement in CA production in S. clavuligerus. This finding reinforces the importance of using this method for productivity improvement.

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Section: Resultsmentioning

confidence: 99%

Enhancement of clavulanic acid production by mutant Streptomyces clavuligerus

Vasconcelos¹

2018

JBMOA

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“…Likewise, an improvement in CA yields using mutagenesis induced by ultraviolet on Streptomyces sp. NRC77 was reported [ 119 ]. The authors found a mutant strain after screening (Streptomyces sp.…”

Section: Regulation Of the Ca Production In S Clavuligementioning

confidence: 99%

Clavulanic Acid Production by Streptomyces clavuligerus: Insights from Systems Biology, Strain Engineering, and Downstream Processing

2021

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Clavulanic acid (CA) is an irreversible β-lactamase enzyme inhibitor with a weak antibacterial activity produced by Streptomyces clavuligerus (S. clavuligerus). CA is typically co-formulated with broad-spectrum β‑lactam antibiotics such as amoxicillin, conferring them high potential to treat diseases caused by bacteria that possess β‑lactam resistance. The clinical importance of CA and the complexity of the production process motivate improvements from an interdisciplinary standpoint by integrating metabolic engineering strategies and knowledge on metabolic and regulatory events through systems biology and multi-omics approaches. In the large-scale bioprocessing, optimization of culture conditions, bioreactor design, agitation regime, as well as advances in CA separation and purification are required to improve the cost structure associated to CA production. This review presents the recent insights in CA production by S. clavuligerus, emphasizing on systems biology approaches, strain engineering, and downstream processing.

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“…However, there are only a few reports on inulinases from streptomyces. It is well known that several Streptomyces species produce a wide variety of useful bioactive metabolites [22][23][24][25][26], including antibiotics, insecticides, and various industrial enzymes of interest.…”

Section: Introductionmentioning

confidence: 99%

Production, purification, and characterization of inulinase from Streptomyces anulatus

Beroigui

Ghadraoui

2023

J Basic Microbiol

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Inulinase is an enzyme that catalyzes inulin to D-fructose. This enzyme can be extracted from plants, but it is difficult to obtain it in large quantities, so its production cost is high. Therefore, microbial inulinase has great potential for industrial needs. In the last decade, there have been very few reports on actinobacterial inulinases, especially on purification and characterization of inulinase process extraction. This study aims to select actinomycetes that possess high inulinase activity from the soil. To screen inulinase-producing bacteria, modified Czapex-Dox agar supplemented with 1% inulin powder was used. The most effective isolate was Streptomyces sp. EFBO8, morphological and genotypic identification methods, confirmed that the strain is Streptomyces anulatus and that its nucleotide sequence has been deposited in GenBank under accession number OQ073700. To optimize inulinase production, kinetics were performed by using S. anulatus strain, which proved to be most productive with a value of 24,024 EU/mL. The enzyme was purified from the culture filtrate by precipitation with ammonium sulfate (NH 4 ) 2 SO 4 , followed by column chromatography Sephadex (G-50) separation. Purified protein has a molecular mass of 3331.83 Da.

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Enhancement of clavulanic acid production by Streptomyces sp MU-NRC77 via mutation and medium optimization

Cited by 8 publications

References 21 publications

Enhancement of clavulanic acid production by mutant Streptomyces clavuligerus

Enhancement of clavulanic acid production by mutant Streptomyces clavuligerus

Clavulanic Acid Production by Streptomyces clavuligerus: Insights from Systems Biology, Strain Engineering, and Downstream Processing

Production, purification, and characterization of inulinase from Streptomyces anulatus

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