Large-scale kinetic metabolic models of Pseudomonas putida KT2440 for consistent design of metabolic engineering strategies

Biotechnology for Biofuels
Milenko TokicLjubisa Miskovic

Abstract

Pseudomonas putida is a promising candidate for the industrial production of biofuels and biochemicals because of its high tolerance to toxic compounds and its ability to grow on a wide variety of substrates. Engineering this organism for improved performances and predicting metabolic responses upon genetic perturbations requires reliable descriptions of its metabolism in the form of stoichiometric and kinetic models. In this work, we developed kinetic models of P. putida to predict the metabolic phenotypes and design metabolic engineering interventions for the production of biochemicals. The developed kinetic models contain 775 reactions and 245 metabolites. Furthermore, we introduce here a novel set of constraints within thermodynamics-based flux analysis that allow for considering concentrations of metabolites that exist in several compartments as separate entities. We started by a gap-filling and thermodynamic curation of iJN1411, the genome-scale model of P. putida KT2440. We then systematically reduced the curated iJN1411 model, and we created three core stoichiometric models of different complexity that describe the central carbon metabolism of P. putida. Using the medium complexity core model as a scaffold, we generated...Continue Reading

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Citations

May 31, 2020·Nature Reviews. Microbiology·Allison J Lopatkin, James J Collins
Dec 29, 2020·Current Opinion in Biotechnology·Charles J FosterCostas D Maranas
Jun 3, 2020·Current Opinion in Biotechnology·Zhixing CaoLixin Zhang
Dec 30, 2020·Microorganisms·Daniel Craig ZielinskiBernhard O Palsson
Apr 1, 2021·Biotechnology Advances·Maria Martin-PascualVitor A P Martins Dos Santos
Apr 26, 2021·Metabolic Engineering·Sophia TsoukaVassily Hatzimanikatis
Apr 20, 2021·Annual Review of Chemical and Biomolecular Engineering·Nick FacklerMichael Köpke

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Methods Mentioned

BETA
gene knockouts

Software Mentioned

matTFA
TFA
BRENDA
lumpGEM
GEM
D2
Flux Balance Analysis ( FBA
iSCHRUNK
ORACLE

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