Scale-down of penicillin production in Penicillium chrysogenumde Jonge, L. P., Buijs, N. A. A., ten Pierick, A., Deshmukh, A., Zhao, Z., Kiel, J. A. K. W., van Gulik, W. M. & Heijnen, J. J., Aug-2011, In : Biotechnology Journal. 6, 8, p. 944-958 15 p.
Research output: Contribution to journal › Article › Academic › peer-review
In large-scale production reactors the combination of high broth viscosity and large broth volume leads to insufficient liquid-phase mixing, resulting in gradients in, for example, the concentrations of substrate and oxygen. This often leads to differences in productivity of the full-scale process compared with laboratory scale. In this scale-down study of penicillin production, the influence of substrate gradients on process performance and cell physiology was investigated by imposing an intermittent feeding regime on a laboratory-scale culture of a high yielding strain of Penicillium chrysogenum. It was found that penicillin production was reduced by a factor of two in the intermittently fed cultures relative to constant feed cultivations fed with the same amount of glucose per hour, while the biomass yield was the same. Measurement of the levels of the intermediates of the penicillin biosynthesis pathway, along with the enzyme levels, suggested that the reduction of the flux through the penicillin pathway is mainly the result of a lower influx into the pathway, possibly due to inhibitory levels of adenosine monophosphate and pyrophosphate and lower activating levels of adenosine triphosphate during the zero-substrate phase of each cycle of intermittent feeding.
|Number of pages||15|
|Publication status||Published - Aug-2011|
- Imperfect mixing, Industrial biotechnology, Intermittent feeding, Pulse feeding, Substrate concentration gradients, DISSOLVED-OXYGEN CONCENTRATION, TANDEM MASS-SPECTROMETRY, IN-VIVO KINETICS, SACCHAROMYCES-CEREVISIAE, DELTA-(L-ALPHA-AMINOADIPYL)-L-CYSTEINYL-D-VALINE SYNTHETASE, INTRACELLULAR METABOLITES, CATABOLITE REPRESSION, QUANTITATIVE-ANALYSIS, PHENYLACETIC ACID, GENE-EXPRESSION