| Dynamic gene expression regulation model for growth and penicillin production in Penicillium chrysogenum. | |
| | |
MedLine Citation:
|
PMID: 20148401 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
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. |
| | |
Authors:
|
Rutger D Douma; Peter J T Verheijen; Wim T A M de Laat; Joseph J Heijnen; Walter M van Gulik |
Publication Detail:
|
Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
|
Title: Biotechnology and bioengineering Volume: 106 ISSN: 1097-0290 ISO Abbreviation: Biotechnol. Bioeng. Publication Date: 2010 Jul |
Date Detail:
|
Created Date: 2010-05-26 Completed Date: 2010-08-17 Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 7502021 Medline TA: Biotechnol Bioeng Country: United States |
Other Details:
|
Languages: eng Pagination: 608-18 Citation Subset: IM |
Affiliation:
|
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 |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Biomass Fungal Proteins / metabolism Gene Expression Regulation, Fungal* Models, Theoretical Oxidoreductases / metabolism Penicillins / biosynthesis* Penicillium chrysogenum / growth & development, metabolism, physiology* |
| Chemical | |
Reg. No./Substance:
|
0/Fungal Proteins; 0/Penicillins; EC 1.-/Oxidoreductases; EC 1.21.3.1/isopenicillin N synthetase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Integrated single-cell analysis shows Pichia pastoris secretes protein stochastically.
Next Document: Collapse temperature of solutions important for lyopreservation of living cells at ambient temperatu...