A study on clavulanic acid production by Streptomyces clavuligerus in batch, fed-batch and continuous processes

Neto, Álvaro Baptista; Hirata, Daniela B.; Filho, L. C. M. Cassiano; Bellão, Carolina; Júnior, A. C. Badino; Hokka, Carlos O.

doi:10.1590/s0104-66322005000400008

Cited by 24 publications

(15 citation statements)

References 8 publications

(5 reference statements)

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“…MU-NRC77 cell growth, the results showing that CA rate production diminished after 96 hours of cultivation. This may be due to the inhibition and repression activity of a product from the metabolism of the microorganism acting on the metabolic pathway of CA production [1]. Production of antimicrobial metabolites from microorganisms requires glycerol as a known important medium component [25].…”

Section: Discussionmentioning

confidence: 99%

“…β-lactam ring-containing molecules such as those of penicillins and cephalosporins were hydrolyzed by the effect of the catalytic ability of enzymes produced by many pathogenic bacteria, resulting in the blocking of their antibacterial property, in turn causing resistance to antibiotics and creating a problem in the treatment of infectious diseases [1]. Clavulanic acid (CA) is a potent ß-Lactamase inhibitor that has been successfully employed in clinical practice.…”

Section: Introductionmentioning

confidence: 99%

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

SAID¹,

Abdelwahed²,

Awad³

et al. 2017

Trop. J. Pharm Res

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

SAID¹,

Abdelwahed²,

Awad³

et al. 2017

Trop. J. Pharm Res

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“…For example, Chen et al [35] obtained 115 mg/l CA from the medium containing soy flour without any addition of amino acids. Neto et al [36] obtained about 200 mg/l using the mixture of complex medium components of soy bean hydrolyzed protein, malt extract, and yeast extract in addition to other minerals. However, all these studies were conducted in a stirred tank bioreactor level with well-controlled conditions.…”

Section: Soil Sample and Isolationmentioning

confidence: 99%

MOLECULAR AND MORPHOLOGICAL IDENTIFICATION OF STREPTOMYCES SP. NRC-88 NOVA SPECIES AS Β-Lactamase INHIBITOR FOR PHARMACEUTICAL APPLICATION

Awad

Germoush

2017

Asian J Pharm Clin Res

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Objective: Clavulanic acid (CA) is a vital agent in the treatment of bacterial infections since it is a potent inhibitor of an extensive variety of β-lactamase enzymes. Its production from Streptomyces strains is fact of expanding clinical significance. This study aimed to isolate and characterize a promising Streptomyces (S) species strain which produced an effective β-lactamase inhibitor.Methods: Streptomyces sp. NRC-88 was isolated from an Egyptian soil sample. The phenotypic and phylogenetic examinations of 16S rRNA gene were investigated. The active metabolite of this strain (CA) was determined by particular synergistic bioassay, spectrophotometric assay, recognized by thin layer chromatography, and structure of the CA affirmed by high-performance liquid chromatography (HPLC) method. Results:A phylogenetic examination of the 16S rRNA gene sequence of the NRC-88 strain consistent with conventional taxonomy was carried out, and confirmed that the strain NRC-88 was most similar to S. aburaviensis S-66 (99%). The active metabolite of this strain (CA) was determined by different methods and confirmed the structure of the CA by the HPLC method. It produced up to 87 mg/l in a specific CA production medium. Conclusion:A new species of Streptomyces sp. NRC-88 isolated and recognized by phenotypic and genotypic proof. This strain suggested the name, Streptomyces sp. NRC-88 (accession number KM014489). It was able to produce CA as the β-lactamase inhibitor.

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“…A porcentagem de variância explicada 90,9 % é aceitável para experimentos biológicos (SHIVHARE e MCCREATH, 2010 clavuligerus (HENAO et al 2012;NETO et al 2005;BELLÃO et al 2013). A produção do AC descrita na literatura é extremamente variável devido à diferença na composição do meio de cultivo, aeração, suplementação do cultivo, pH e temperatura de cultivo (SER et al 2016).…”

Section: Fonteunclassified

Determinação Do Ph E Temperatura Ótimos Para a Produtividade Do Ácido Clavulânico Utilizando O Streptomyces Clavuligerus Atcc 27064

Pinelli¹,

Dias²

2017

MUNDI ETG

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Determinação do pH e temperatura ótimos para a produtividade do ácido clavulânico utilizando o Streptomyces clavuligerus ATCC 27064Determination of pH and temperature optimum on the productivity of clavulanic acid using Streptomyces clavuligerus ATCC 27064Juliana Junqueira Pinelli 1 Sandra de Cássia Dias 2 Resumo: O ácido clavulânico (AC) é um metabólito secundário produzido pela bactéria GramPositiva Streptomyces clavuligerus. É um composto de suma importância, principalmente para a indústria farmacêutica, pois possui ação antibacteriana. É utilizado em associação com outros antibióticos, como a amoxicilina. Sua produção ocorre por via fermentativa. O pH e a temperatura do meio são parâmetros relevantes que podem comprometer a produção deste metabólito. O presente trabalho teve como objetivo avaliar a influência da temperatura e do pH na produção de ácido clavulânico a partir de Streptomyces clavuligerus ATCC 27064. Para isso, um número mínimo de experimentos foi desenhado com diferentes valores de pH e temperatura utilizando o planejamento experimental estatístico, delineamento composto central rotacional, DCCR, tendo como variáveis pH e temperatura e como resposta a produtividade do ácido clavulânico. Amostras foram retiradas a cada 12 horas e a produção de ácido clavulânico determinada por método espectrofotométrico. O cultivo realizado em pH 6,7 e temperatura 27ºC apresentou maior produtividade do ácido clavulânico. Palavras-chave:Delineamento composto central rotacional. Antibiótico. Metodologia de superfície de resposta. Bioprocessos Abstract: Clavulanic acid (CA) is a secondary metabolite produced by the Gram-Positive bacteria Streptomyces clavuligerus. It is a compound of great importance, mainly for the pharmaceutical industry, because it has antibacterial activity. It is used in combination with other antibiotics such as amoxicillin. Its production occurs by fermentation. The pH and temperature of the medium are relevant parameters that can compromise the production of this metabolite. The aim of this study was to evaluate the temperature and pH influence on the clavulanic acid productivity by Streptomyces clavuligerus ATCC 27064. For this, a minimum number of experiments were designed with different values of pH and temperature using statistical experimental design, central composite rotational design (CCRD) having as variables pH and temperature and as response the clavulanic acid productivity. Samples were collected every 12 hours and the clavulanic acid production was determined by spectrophotometric method. The cultivation carried out at pH 6.7 and temperature 27ºC showed the highest clavulanic acid productivity.

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A study on clavulanic acid production by Streptomyces clavuligerus in batch, fed-batch and continuous processes

Cited by 24 publications

References 8 publications

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

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

MOLECULAR AND MORPHOLOGICAL IDENTIFICATION OF STREPTOMYCES SP. NRC-88 NOVA SPECIES AS Β-Lactamase INHIBITOR FOR PHARMACEUTICAL APPLICATION

Determinação Do Ph E Temperatura Ótimos Para a Produtividade Do Ácido Clavulânico Utilizando O Streptomyces Clavuligerus Atcc 27064

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