Linking genes to microbial growth kinetics: an integrated biochemical systems engineering approach.
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Authors
Koutinas, MichalisKiparissides, Alexandros
Silva-Rocha, Rafael
Lam, Ming-Chi
Martins Dos Santos, Vitor A P
de Lorenzo, Victor
Pistikopoulos, Efstratios N
Mantalaris, Athanasios
Issue Date
2011-07
Metadata
Show full item recordAbstract
The majority of models describing the kinetic properties of a microorganism for a given substrate are unstructured and empirical. They are formulated in this manner so that the complex mechanism of cell growth is simplified. Herein, a novel approach for modelling microbial growth kinetics is proposed, linking biomass growth and substrate consumption rates to the gene regulatory programmes that control these processes. A dynamic model of the TOL (pWW0) plasmid of Pseudomonas putida mt-2 has been developed, describing the molecular interactions that lead to the transcription of the upper and meta operons, known to produce the enzymes for the oxidative catabolism of m-xylene. The genetic circuit model was combined with a growth kinetic model decoupling biomass growth and substrate consumption rates, which are expressed as independent functions of the rate-limiting enzymes produced by the operons. Estimation of model parameters and validation of the model's predictive capability were successfully performed in batch cultures of mt-2 fed with different concentrations of m-xylene, as confirmed by relative mRNA concentration measurements of the promoters encoded in TOL. The growth formation and substrate utilisation patterns could not be accurately described by traditional Monod-type models for a wide range of conditions, demonstrating the critical importance of gene regulation for the development of advanced models closely predicting complex bioprocesses. In contrast, the proposed strategy, which utilises quantitative information pertaining to upstream molecular events that control the production of rate-limiting enzymes, predicts the catabolism of a substrate and biomass formation and could be of central importance for the design of optimal bioprocesses.Citation
Linking genes to microbial growth kinetics: an integrated biochemical systems engineering approach. 2011, 13 (4):401-13 Metab. Eng.Affiliation
Centre for Process Systems Engineering, Department of Chemical Engineering, South Kensington Campus, Imperial College London, UK.Journal
Metabolic engineeringPubMed ID
21315172Type
ArticleLanguage
enISSN
1096-7184ae974a485f413a2113503eed53cd6c53
10.1016/j.ymben.2011.02.001
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