scholarly journals Degradation Kinetics of Clavulanic Acid in Fermentation Broths at Low Temperatures

Antibiotics ◽  
2019 ◽  
Vol 8 (1) ◽  
pp. 6 ◽  
Author(s):  
David Gómez-Ríos ◽  
Howard Ramírez-Malule ◽  
Peter Neubauer ◽  
Stefan Junne ◽  
Rigoberto Ríos-Estepa

Clavulanic acid (CA) is a β-lactam antibiotic inhibitor of β-lactamase enzymes, which confers resistance to bacteria against several antibiotics. CA is produced in submerged cultures by the filamentous Gram-positive bacterium Streptomyces clavuligerus; yield and downstream process are compromised by a degradation phenomenon, which is not yet completely elucidated. In this contribution, a study of degradation kinetics of CA at low temperatures (−80, −20, 4, and 25 °C) and pH 6.8 in chemically-defined fermentation broths is presented. Samples of CA in the fermentation broths showed a fast decline of concentration during the first 5 h followed by a slower, but stable, reaction rate in the subsequent hours. A reversible-irreversible kinetic model was applied to explain the degradation rate of CA, its dependence on temperature and concentration. Kinetic parameters for the equilibrium and irreversible reactions were calculated and the proposed kinetic model was validated with experimental data of CA degradation ranging 16.3 mg/L to 127.0 mg/L. Degradation of the chromophore CA-imidazole, which is commonly used for quantifications by High Performance Liquid Chromatography, was also studied at 4 °C and 25 °C, showing a rapid rate of degradation according to irreversible first-order kinetics. A hydrolysis reaction mechanism is proposed as the cause of CA-imidazole loss in aqueous solutions.

2011 ◽  
Vol 399-401 ◽  
pp. 1067-1070
Author(s):  
Chun Yan Li ◽  
Cong Cong Hu ◽  
Zhi Guo Wen ◽  
Sheng Xiong Dong

The method of high performance liquid chromatography (HPLC) is established to determine the content of antibacterial agent — ciprofloxacin (CF) in the degradation solution of ciprofloxacin-polyurethane (CFPU) and investigate the in vitro degradation kinetics by plotting and fitting the cumulative release curves to inspect the effects of different medium and different concentrations on drug release. The results showed that the HPLC method is accurate, reliable and simple. The drug-release of CFPU was bioresponsive and could be accorded with first order kinetics. It was observed that CF was released from CFPU by a combination of diffusion and erosion mechanism, mainly in the manner of diffusion in the absence of infection while erosion mechanism in the presence of infection.


2016 ◽  
Vol 120 ◽  
pp. 241-247 ◽  
Author(s):  
Howard Ramirez-Malule ◽  
Stefan Junne ◽  
Carlos López ◽  
Julian Zapata ◽  
Alex Sáez ◽  
...  

Polymers ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 1577
Author(s):  
Aditya Ramgobin ◽  
Gaëlle Fontaine ◽  
Serge Bourbigot

Kinetic decomposition models for the thermal decomposition of a high-performance polymeric material (polyetheretherketone, PEEK) were determined from specific techniques. Experimental data from thermogravimetric analysis (TGA) and previously elucidated decomposition mechanisms were combined with a numerical simulating tool to establish a comprehensive kinetic model for the decomposition of PEEK under three atmospheres: nitrogen, 2% oxygen, and synthetic air. Multistepped kinetic models with subsequent and competitive reactions were established by taking into consideration the different types of reactions that may occur during the thermal decomposition of the material (chain scission, thermo-oxidation, char formation). The decomposition products and decomposition mechanism of PEEK which were established in our previous report allowed for the elucidation of the kinetic decomposition models. A three-stepped kinetic thermal decomposition pathway was a good fit to model the thermal decomposition of PEEK under nitrogen. The kinetic model involved an autocatalytic type of reaction followed by competitive and successive nth order reactions. Such types of models were set up for the evaluation of the kinetics of the thermal decomposition of PEEK under 2% oxygen and in air, leading to models with satisfactory fidelity.


2015 ◽  
Vol 14 (2) ◽  
pp. 366-377 ◽  
Author(s):  
Eduardo Vidal ◽  
Antonio Negro ◽  
Alberto Cassano ◽  
Cristina Zalazar

This work reports the degradation kinetics of glyphosate in water employing the UV/H2O2process. The kinetic model was experimentally validated. Results compare the kinetics of the herbicide alone and a commercial formulation.


2021 ◽  
Vol 14 (4) ◽  
pp. 2357-2368
Author(s):  
Ke Meng ◽  
Xiao Wang ◽  
Zhimin Li ◽  
Zhou Liu ◽  
Zhi Qiao ◽  
...  

Inspired and guided by the structural characteristics and degradation kinetics of a low-dimensional perovskite (LDP) film, an effective self-passivation strategy is proposed to fabricate the high-performance LDP based solar cells.


Author(s):  
Isara Lourdes Cruz-Hernández ◽  
Eliton Da Silva Vasconcelos ◽  
Juliana Conceição Teodoro ◽  
Alvaro De Baptista-Neto ◽  
Maria Lucia Gonsales Da Costa Araujo ◽  
...  

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 the wild strain Streptomyces clavuligerus ATCC 27064. Submerged cultures were performed, with the best mutants selected, in a 5L bench-scale bioreactor, batch-wise, utilizing a complex medium containing glycerol and a soybean protein isolate as the main components. The mutant 70 was able to produce a maximum CA concentration of 500 mg.L-1, approximately 1.6 times higher than the wild strain. Another finding was a higher CA productivity of 29.5 mg.h-1.L-1 with this mutant, although a lower specific growth rate had been observed.


2016 ◽  
Vol 99 (6) ◽  
pp. 1505-1512
Author(s):  
Kunjan Bharatkumar Bodiwala ◽  
Shailesh Shah ◽  
Jeenal Thakor ◽  
Bhavin Marolia ◽  
Pintu Prajapati

Abstract A rapid, sensitive, and stability-indicating high-performance thin-layer chromatographic method was developed and validated to study degradation kinetics of Alogliptin benzoate (ALG) in an alkaline medium. ALG was degraded under acidic, alkaline, oxidative, and thermal stress conditions. The degraded samples were chromatographed on silica gel 60F254-TLC plates, developed using a quaternary-solvent system (chloroform–methanol–ethyl acetate–triethyl amine, 9+1+1+0.5, v/v/v/v), and scanned at 278 nm. The developed method was validated per International Conference on Harmonization guidelines using validation parameters such as specificity, linearity and range, precision, accuracy, LOD, and LOQ. The linearity range for ALG was 100–500 ng/band (correlation coefficient = 0.9997) with an average recovery of 99.47%. The LOD and LOQ for ALG were 9.8 and 32.7 ng/band, respectively. The developed method was successfully applied for the quantitative estimation of ALG in its synthetic mixture with common excipients. Degradation kinetics of ALG in an alkaline medium was studied by degrading it under three different temperatures and three different concentrations of alkali. Degradation of ALG in the alkaline medium was found to follow first-order kinetics. Contour plots have been generated to predict degradation rate constant, half-life, and shelf life of ALG in various combinations of temperature and concentration of alkali using Design Expert software.


2002 ◽  
Vol 184 (23) ◽  
pp. 6559-6565 ◽  
Author(s):  
Alvaro de la Fuente ◽  
Luis M. Lorenzana ◽  
Juan F. Martín ◽  
Paloma Liras

ABSTRACT A Streptomyces clavuligerus ccaR::aph strain, which has a disruption in the regulatory gene ccaR, does not produce cephamycin C or clavulanic acid, but does produce a bioactive compound that was identified as holomycin by high-performance liquid chromatography (HPLC) and infrared and mass spectrometry. S. clavuligerus strains with disruptions in different genes of the clavulanic acid pathway fall into three groups with respect to holomycin biosynthesis. (i) Mutants with mutations in the early steps of the pathway blocked in the gene ceaS (pyc) (encoding carboxyethylarginine synthase), bls (encoding a β-lactam synthetase), or open reading frame 6 (ORF6; coding for an acetyltransferase of unknown function) are holomycin nonproducers. (ii) Mutants blocked in the regulatory gene ccaR or claR or blocked in the last gene of the pathway encoding clavulanic acid reductase (car) produce holomycin at higher levels than the wild-type strain. (iii) Mutants with disruption in cyp (coding for cytochrome P450), ORF12, and ORF15, genes that appear to be involved in the conversion of clavaminic acid into clavaldehyde or in secretion steps, produce up to 250-fold as much holomycin as the wild-type strain. An assay for holomycin synthetase was developed. This enzyme forms holomycin from holothin by using acetyl coenzyme A as an acetyl group donor. The holomycin synthase activities in the different clavulanic acid mutants correlate well with their production of holomycin.


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