Data of clavulanic acid and clavulanate-imidazole stability at low temperatures

Abstract

Clavulanic acid (CA) is a β-lactam antibiotic with a strong inhibitory effect on β-lactamase enzymes. CA is produced in submerged cultures by the filamentous Gram-positive bacterium Streptomyces clavuligerus (S. clavuligerus). CA is an unstable molecule in aqueous solution and its stability depends strongly on temperature and concentration. In this contribution, the experimental data of CA stability, produced in chemically defined media and exposed to temperatures between −80 and 25 °C, are presented. The chromophore clavulanate-imidazole (CAI) is commonly used for analysis and quantification of CA samples by High Performance Liquid Chromatography (HPLC); nevertheless, this molecule is also susceptible to suffer degradation in aqueous solution, potentially affecting the quantification of CA. Data of CAI concentration for samples conserved at 4 °C and 25 °C are also presented. A reversible-irreversible kinetic model was applied to estimate the degradation rate of CA. Data from numerical simulations of CA degradation using the proposed kinetic model are also graphically presented. The data show the clavulanic acid instability in fermentation broths, in a range of temperatures of interest for bioprocess operation, downstream processing, samples quantification, conservation and storage.

A Genome-Scale Insight into the Effect of Shear Stress During the Fed-Batch Production of Clavulanic Acid by Streptomyces Clavuligerus

“…CA is usually produced in submerged cultures under appropriate nutritional conditions. However, CA is unstable in aqueous solutions including fermentation broths and its productivity is compromised in both production and downstream processes [ 2 , 3 ]. Several studies have focused on assessing the effect of nutrients and environmental conditions on CA production and have identified a variety of operational conditions that presumably favor its accumulation during the cultivation process, as previously reviewed by Ser et al [ 4 ].…”

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

“…Shear conditions in CA production has been previously explored in airlifts [3] and stirred tank reactors [4]; however, the physiological response of S. clavuligerus to shear forces and its relationship with CA secretion is not completely understood. Many efforts have been carried out to increase the yield of CA since not only nutritional, but also environmental and degradation factors compromise the product yield in submerged cultivations of S. clavuligerus [5,6]. Several studies focused on the effect of nutrient concentrations and environmental cultivation conditions on CA biosynthesis, as Ser et al [7] reviewed.…”

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

“…Several authors have confirmed the degradation of CA in fermentation broths [67,69,[168][169][170], synthetic buffer [68,171,172], and pure water [173][174][175]. The CA secreted by S. clavuligerus exhibits a high initial reaction rate (~5 h) in aqueous solution (e.g., fermentation broths) followed by a slower degradation rate in the next hours [168,169]. Degradation of CA is considered consequence of susceptibility to nucleophilic attacks at specific points.…”

“…In addition to the characteristic low productivity of the bioprocess, the product yield is also compromised by the degradation of CA in aqueous phases and the efficiency of the separation steps required for the obtention of potassium clavulanate (the stable commercial form). Several authors have confirmed the degradation of CA in fermentation broths [ 67 , 69 , 168 , 169 , 170 ], synthetic buffer [ 68 , 171 , 172 ], and pure water [ 173 , 174 , 175 ]. The CA secreted by S. clavuligerus exhibits a high initial reaction rate (~5 h) in aqueous solution (e.g., fermentation broths) followed by a slower degradation rate in the next hours [ 168 , 169 ].…”