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dc.contributor.authorLázaro, Jorge
dc.contributor.authorJansen, Giorgio
dc.contributor.authorYang, Yiheng
dc.contributor.authorTorres-Acosta, Mario A
dc.contributor.authorLye, Gary
dc.contributor.authorOliver, Stephen G
dc.contributor.authorJúlvez, Jorge
dc.description.abstractThe current production of a number of commodity chemicals relies on the exploitation of fossil fuels and hence has an irreversible impact on the environment. Biotechnological processes offer an attractive alternative by enabling the manufacturing of chemicals by genetically modified microorganisms. However, this alternative approach poses some important technical challenges that must be tackled to make it competitive. On the one hand, the design of biotechnological processes is based on trial-and-error approaches, which are not only costly in terms of time and money, but also result in suboptimal designs. On the other hand, the manufacturing of chemicals by biological processes is almost exclusively carried out by batch or fed-batch cultures. Given that batch cultures are expensive and not easy to scale, technical means must be developed to make continuous cultures feasible and efficient. In order to address these challenges, we have developed a mathematical model able to integrate in a single model both the genome-scale metabolic model for the organism synthesizing the chemical of interest and the dynamics of the bioreactor in which the organism is cultured. Such a model is based on the use of Flexible Nets, a modeling formalism for dynamical systems. The integration of a microscopic (organism) and a macroscopic (bioreactor) model in a single net provides an overall view of the whole system and opens the door to global optimizations. As a case study, the production of citramalate with respect to the substrate consumed by E. coli is modeled, simulated and optimized in order to find the maximum productivity in a steady-state continuous culture. The predicted computational results were consistent with the wet lab experiments.
dc.description.sponsorshipBiological Sciences Research Council (UK) grant no. BB/N02348X/1, as part of the IBiotech Program, and by the Industrial Biotechnology Catalyst (Innovate UK, BBSRC, EPSRC) to support the translation, development and commercialisation of innovative Industrial Biotechnology processes.
dc.publisherFrontiers Media SA
dc.rightsAttribution 4.0 International
dc.subjectcitramalate production
dc.subjectcommodity chemicals
dc.subjectcontinuous culture
dc.subjectflexible nets
dc.subjectgenome-scale models
dc.subjectmodel integration
dc.subjectmodeling formalisms
dc.subjectmulti-scale models
dc.titleCombination of Genome-Scale Models and Bioreactor Dynamics to Optimize the Production of Commodity Chemicals.
dc.publisher.departmentDepartment of Biochemistry
prism.publicationNameFront Mol Biosci
dc.contributor.orcidOliver, Stephen [0000-0001-6330-7526]
rioxxterms.typeJournal Article/Review
pubs.funder-project-idBiotechnology and Biological Sciences Research Council (BB/N02348X/1)
cam.orpheus.success2022-03-08 - Embargo set during processing via Fast-track
pubs.licence-display-nameApollo Repository Deposit Licence Agreement

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Attribution 4.0 International
Except where otherwise noted, this item's licence is described as Attribution 4.0 International