The Influence of oxygen concentration and of specific rate of growth on the kinetics of Penicillin production

Giona, A. R.; Santis, Roberto De; Marrelli, Luigi; Toro, León F.

doi:10.1002/bit.260180405

Cited by 9 publications

(2 citation statements)

References 6 publications

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“…The biomass produced during the growth phase should be as high as possible to obtain afterwards a high productivity. The optimal initial substrate supply and the maximum reachable cell mass is to a great extent determined by the maximum oxygen transfer rate of the reactor [ 11,32,61,80,81 ]. Depending on the growth kinetics, the boundary conditions and performance criterion for the optimization, the ideal optimal control can require additional phases.…”

Section: Application Of the Model To Process Optimizationmentioning

confidence: 99%

Proces models for production of β-lactam antibiotics

Bellgardt

1998

Relation Between Morphology and Process Performances

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Great progress has been made in the modelling of biotechnical processes using filamentous microorganisms. This paper deals with cultivations of Penicillium chrysogenum for the production of Penicillin and of Acrernonium chrysogenum for the production of Cephalosporin C. The properties of the processes and the existing models are reviewed. Models are presented for both processes that consider aspects which are important for industrial cultivation. The process model for Penicillin production is based on a detailed morphological description of growth of hyphal filaments and pellets. The model allows for simulation of the production process including the preculture and considering the inhomogenous pellet population. It opens new possibilities for understanding the complex kinetics of the process and improvement of its control. The structured segregated model for Cephalosporin C production considers soy oil as second carbon source besides sugar. The application of the model for dynamic optimization of feeding strategies by Iterative Dynamic Programming is demonstrated. As an alternative approach, modelling of the Cephalosporin production by an artificial neural network is discussed.

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Section: Application Of the Model To Process Optimizationmentioning

confidence: 99%

Proces models for production of β-lactam antibiotics

Bellgardt

1998

Relation Between Morphology and Process Performances

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“…To promote product formation over biomass production, most industrial production processes are operated in multistage fed-batch modes. Investigation of fed-batch bioprocesses for Penicillium chrysogenum was an active field of research until the early 90s [1][2][3][4][5][6][7][8][9][10][11][12] and was thoroughly summarized approximately 15 years ago. 13,14 Subsequently, the advancement of quantitative biochemical analytical techniques has led the scientific community to focus on the investigation of the organism's metabolism and its regulation rather than continuing investigation of the industrial process.…”

Section: Introductionmentioning

confidence: 99%

Physiological description of multivariate interdependencies between process parameters, morphology and physiology during fed‐batch penicillin production

Posch¹,

Herwig²

2014

Biotechnology Progress

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Optimization of productivity and economics of industrial bioprocesses requires characterization of interdependencies between process parameters and process performance. In the case of penicillin production, as in other processes, process performance is often closely interlinked with the physiology and morphology of the organism used for production. This study presents a systematic approach to efficiently characterize the physiological effects of multivariate interdependencies between bioprocess design parameters (spore inoculum concentration, pO2 control level and substrate feed rate), morphology, and physiology. Method development and application was performed using the industrial model process of penicillin production. Applying traditional, statistical bioprocess analysis, multivariate correlations of raw bioprocess design parameters (high spore inoculum concentration, low pO2 control as well as reduced glucose feeding) and pellet morphology were identified. A major drawback of raw design parameter correlation models; however, is the lack of transferability across different process scales and regimes. In this context, morphological and physiological bioprocess modeling based on scalable physiological parameters is introduced. In this study, raw parameter effects on pellet morphology were efficiently summarized by the physiological parameter of the biomass yield per substrate. Finally, for the first time to our knowledge, the specific growth rate per spore was described as time-independent determinant for switching from pellet to disperse growth during penicillin production and thus introduced as a novel, scalable key process parameter for pellet morphology and process performance.

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Instabilities of product formation in a fed‐batch culture of Penicillium chrysogenum

Hegewald¹,

Wolleschensky²,

Guthke

et al. 1981

Biotech & Bioengineering

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SummaryBy investigation of a model of benzylpenicillin fermentation it was demonstrated that high fermentation productivity is connected with low stability. The increasing instability is not the result of external disturbances but of peculiarities inherent to the system. The main process variables and the essential parameters were selected by analysis of data obtained from fermentation runs in a pilot plant. By simulation on an analog computer it was shown that the proposed model gives a sufficient description of the kinetic behavior of the fermentation runs. By varying the initial conditions it was possible to obtain two types of fermentation runs. One type is distinguished by a high productivity connected with low initial concentrations of sucrose. An increase of the initial sucrose concentration also causes an increase of productivity. When a certain value of this concentration is exceeded a changeover to a faster growth of biomass takes place combined with the breakdown of productivity. The same phenomenon occurs at a defined initial concentration of sucrose if a disturbance of oxygen transfer rate takes place. Whether the culture stays in the one or in the other state after the disturbance has passed depends on the duration, the strength, and the beginning of the disturbance. In the pilot plant similar behavior can be observed. The sensitivity of fermentation processes to disturbances increases with the increase of productivity.

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The Influence of oxygen concentration and of specific rate of growth on the kinetics of Penicillin production

Cited by 9 publications

References 6 publications

Proces models for production of β-lactam antibiotics

Proces models for production of β-lactam antibiotics

Physiological description of multivariate interdependencies between process parameters, morphology and physiology during fed‐batch penicillin production

Instabilities of product formation in a fed‐batch culture of Penicillium chrysogenum

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