High concentrations of clavulanic acid but not of its degradation products decrease glycerol consumption and oxygen uptake rates in cultures of Streptomyces clavuligerus

Biotechnology and Bioengineering
Simone BrethauerSven Panke

Abstract

Product inhibition of biological production systems is a widely observed phenomenon with prominent implications for the design and ultimately the success of biotechnological processes. In order to investigate whether such effects could limit the maximal concentrations in the production of the beta-lactamase inhibitor clavulanic acid (CA) in Streptomyces clavuligerus cultivations under process-related conditions, we first validated the equivalence of a laboratory scale aerated stirred tank reactor and a medium scale (50 mL) cultivation device, which required optimization of gas transfer in the latter and finally allowed to conduct the required experiments in smaller volumes with correspondingly reduced consumption of compounds. With this, we investigated the effect of CA additions on two global performance parameters: consumption of the carbon source glycerol and oxygen consumption (measured as the oxygen uptake rate, OUR). Increased levels of CA severely interfered with the physiology of the producing strain at least at and above 1.6 g L(-1) CA, as indicated by a dose-dependent decrease in maximal OURs and glycerol consumption rates. As CA is rapidly degraded during cultivation, it was unclear whether CA itself or its decomposi...Continue Reading

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Mar 29, 2007·Biotechnology and Bioengineering·Simone BrethauerSven Panke

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Citations

Jan 1, 2010·Acta Crystallographica. Section E, Structure Reports Online·Kotaro FujiiSlamet Ibrahim

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