Clavulanic Acid Degradation in Streptomyces clavuligerus Fed‐Batch Cultivations

Biotechnology Progress - Tập 18 Số 3 - Trang 451-457 - 2002
Johannes A. Roubos1, Preben Krabben, W. T. A. M. De Laat, Robert Babuška, Joseph J. Heijnen
1Control Systems Engineering, Faculty of Information Technology and Systems, Delft University of Technology, P.O. Box 5031, 2600 GA Delft, The Netherlands. [email protected].

Tóm tắt

AbstractClavulanic acid (CA) is an important antibiotic that is produced by Streptomyces clavuligerus. CA is unstable and product degradation has turned out to have a major impact on product titers in fed‐batch cultivations. Three different types of experiments have been used to elucidate CA degradation under fed‐batch cultivation conditions. First, the influence of individual medium compounds was examined. Second, degradation was monitored during the exponential growth phase in batch cultivations. Third, CA degradation was studied in the supernatant of samples taken during a fed‐batch. In addition, data from six fed‐batch cultivations were studied to derive information about CA degradation during the production phase. These cultivations were based on a mineral medium, containing glycerol, glutamate, ammonium, and phosphate as the main nutrients. The ammonium concentration had a large influence on the degradation rate constant. In addition, either changes in the substrate availability or high concentrations of ammonium or glycerol cause a major increase in the degradation rate constant. Finally, a linear and a fuzzy logic model were made to predict CA degradation rates in these fed‐batches.

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Biotechnology Progress

Tập 18 Số 3

451-457

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