Dynamic gene expression regulation model for growth and penicillin production in Penicillium chrysogenum. 2010

Rutger D Douma, and Peter J T Verheijen, and Wim T A M de Laat, and Joseph J Heijnen, and Walter M van Gulik
Department of Biotechnology, Delft University of Technology, Kluyver Centre for Genomics of Industrial Fermentation, Julianalaan 67, 2628 BC Delft, The Netherlands. r.d.douma@tudelft.nl

As is often the case for microbial product formation, the penicillin production rate of Penicillium chrysogenum has been observed to be a function of the growth rate of the organism. The relation between the biomass specific rate of penicillin formation (q(p)) and growth rate (mu) has been measured under steady state conditions in carbon limited chemostats resulting in a steady state q(p)(mu) relation. Direct application of such a relation to predict the rate of product formation during dynamic conditions, as they occur, for example, in fed-batch experiments, leads to errors in the prediction, because q(p) is not an instantaneous function of the growth rate but rather lags behind because of adaptational and regulatory processes. In this paper a dynamic gene regulation model is presented, in which the specific rate of penicillin production is assumed to be a linear function of the amount of a rate-limiting enzyme in the penicillin production pathway. Enzyme activity assays were performed and strongly indicated that isopenicillin-N synthase (IPNS) was the main rate-limiting enzyme for penicillin-G biosynthesis in our strain. The developed gene regulation model predicts the expression of this rate limiting enzyme based on glucose repression, fast decay of the mRNA encoding for the enzyme as well as the decay of the enzyme itself. The gene regulation model was combined with a stoichiometric model and appeared to accurately describe the biomass and penicillin concentrations for both chemostat steady-state as well as the dynamics during chemostat start-up and fed-batch cultivation.

UI MeSH Term Description Entries
D008962 Models, Theoretical Theoretical representations that simulate the behavior or activity of systems, processes, or phenomena. They include the use of mathematical equations, computers, and other electronic equipment. Experimental Model,Experimental Models,Mathematical Model,Model, Experimental,Models (Theoretical),Models, Experimental,Models, Theoretic,Theoretical Study,Mathematical Models,Model (Theoretical),Model, Mathematical,Model, Theoretical,Models, Mathematical,Studies, Theoretical,Study, Theoretical,Theoretical Model,Theoretical Models,Theoretical Studies
D010088 Oxidoreductases The class of all enzymes catalyzing oxidoreduction reactions. The substrate that is oxidized is regarded as a hydrogen donor. The systematic name is based on donor:acceptor oxidoreductase. The recommended name will be dehydrogenase, wherever this is possible; as an alternative, reductase can be used. Oxidase is only used in cases where O2 is the acceptor. (Enzyme Nomenclature, 1992, p9) Dehydrogenases,Oxidases,Oxidoreductase,Reductases,Dehydrogenase,Oxidase,Reductase
D010406 Penicillins A group of antibiotics that contain 6-aminopenicillanic acid with a side chain attached to the 6-amino group. The penicillin nucleus is the chief structural requirement for biological activity. The side-chain structure determines many of the antibacterial and pharmacological characteristics. (Goodman and Gilman's The Pharmacological Basis of Therapeutics, 8th ed, p1065) Antibiotics, Penicillin,Penicillin,Penicillin Antibiotics
D010408 Penicillium chrysogenum A mitosporic fungal species used in the production of penicillin. Penicillium chrysogeum,Penicillium notatum
D005656 Fungal Proteins Proteins found in any species of fungus. Fungal Gene Products,Fungal Gene Proteins,Fungal Peptides,Gene Products, Fungal,Yeast Proteins,Gene Proteins, Fungal,Peptides, Fungal,Proteins, Fungal
D015966 Gene Expression Regulation, Fungal Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in fungi. Fungal Gene Expression Regulation,Regulation of Gene Expression, Fungal,Regulation, Gene Expression, Fungal
D018533 Biomass Total mass of all the organisms of a given type and/or in a given area. (From Concise Dictionary of Biology, 1990) It includes the yield of vegetative mass produced from any given crop. Biomasses

Related Publications

Rutger D Douma, and Peter J T Verheijen, and Wim T A M de Laat, and Joseph J Heijnen, and Walter M van Gulik
October 2007, FEMS yeast research,
Rutger D Douma, and Peter J T Verheijen, and Wim T A M de Laat, and Joseph J Heijnen, and Walter M van Gulik
September 1996, Biotechnology and bioengineering,
Rutger D Douma, and Peter J T Verheijen, and Wim T A M de Laat, and Joseph J Heijnen, and Walter M van Gulik
September 1995, Journal of biotechnology,
Rutger D Douma, and Peter J T Verheijen, and Wim T A M de Laat, and Joseph J Heijnen, and Walter M van Gulik
January 1993, Applied biochemistry and biotechnology,
Rutger D Douma, and Peter J T Verheijen, and Wim T A M de Laat, and Joseph J Heijnen, and Walter M van Gulik
August 2011, Biotechnology journal,
Rutger D Douma, and Peter J T Verheijen, and Wim T A M de Laat, and Joseph J Heijnen, and Walter M van Gulik
May 1973, Journal of general microbiology,
Rutger D Douma, and Peter J T Verheijen, and Wim T A M de Laat, and Joseph J Heijnen, and Walter M van Gulik
November 2010, Applied and environmental microbiology,
Rutger D Douma, and Peter J T Verheijen, and Wim T A M de Laat, and Joseph J Heijnen, and Walter M van Gulik
December 1991, Annals of the New York Academy of Sciences,
Rutger D Douma, and Peter J T Verheijen, and Wim T A M de Laat, and Joseph J Heijnen, and Walter M van Gulik
January 2001, Biotechnology and bioengineering,
Rutger D Douma, and Peter J T Verheijen, and Wim T A M de Laat, and Joseph J Heijnen, and Walter M van Gulik
November 1967, Journal of bacteriology,
Copied contents to your clipboard!