Linking genes to microbial growth kinetics: an integrated biochemical systems engineering approach.
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Martins Dos Santos, Vitor A P
de Lorenzo, Victor
Pistikopoulos, Efstratios N
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AbstractThe 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.
CitationLinking genes to microbial growth kinetics: an integrated biochemical systems engineering approach. 2011, 13 (4):401-13 Metab. Eng.
AffiliationCentre for Process Systems Engineering, Department of Chemical Engineering, South Kensington Campus, Imperial College London, UK.
The following license files are associated with this item:
- The regulatory logic of m-xylene biodegradation by Pseudomonas putida mt-2 exposed by dynamic modelling of the principal node Ps/Pr of the TOL plasmid.
- Authors: Koutinas M, Lam MC, Kiparissides A, Silva-Rocha R, Godinho M, Livingston AG, Pistikopoulos EN, de Lorenzo V, Dos Santos VA, Mantalaris A
- Issue date: 2010 Jun
- The logic layout of the TOL network of Pseudomonas putida pWW0 plasmid stems from a metabolic amplifier motif (MAM) that optimizes biodegradation of m-xylene.
- Authors: Silva-Rocha R, de Jong H, Tamames J, de Lorenzo V
- Issue date: 2011 Nov 11
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- Issue date: 2005 Sep
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- Optimal bioprocess design through a gene regulatory network - Growth kinetic hybrid model: Towards replacing Monod kinetics.
- Authors: Tsipa A, Koutinas M, Usaku C, Mantalaris A
- Issue date: 2018 Jul