title: Identification of line-specific strategies for improving carotenoid production in synthetic maize through data-driven mathematical modeling.
abstract: Plant synthetic biology is still in its infancy. However, synthetic biology approaches have been used to manipulate and improve the nutritional and health value of staple food crops such as rice, potato and maize. With current technologies, production yields of the synthetic nutrients are a result of trial and error, and systematic rational strategies to optimize those yields are still lacking. Here, we present a workflow that combines gene expression and quantitative metabolomics with mathematical modeling to identify strategies for increasing production yields of nutritionally important carotenoids in the seed endosperm synthesized through alternative biosynthetic pathways in synthetic lines of white maize, which is normally devoid of carotenoids. Quantitative metabolomics and gene expression data are used to create and fit parameters of mathematical models that are specific to four independent maize lines. Sensitivity analysis and simulation of each model is used to predict which gene activities should be further engineered in order to increase production yields for carotenoid accumulation in each line. Some of these predictions (e.g. increasing Zmlycb/Gllycb will increase accumulated β-carotenes) are valid across the four maize lines and consistent with experimental observations in other systems. Other predictions are line specific. The workflow is adaptable to any other biological system for which appropriate quantitative information is available. Furthermore, we validate some of the predictions using experimental data from additional synthetic maize lines for which no models were developed.
authors.affiliation: Departament de Ciencies Mèdiques Bàsiques, Universitat de Lleida, Lleida, Spain.|Institut de Recerca Biomèdica de Lleida IRBLLeida, Edifici de Recerca Biomédica I, Av Rovira Roure 80, Lleida, Catalunya, 25198, Spain.|Computer Science Department and INSPIRES, University of Lleida, Jaume II 69, Lleida, Catalunya, 25001, Spain.
authors.forename: Jorge
authors.initials: J
authors.lastname: Comas
authors.affiliation: Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, 3004-517, Portugal.|Institute for Interdisciplinary Research, University of Coimbra, Coimbra, 3030-789, Portugal.
authors.forename: Rui
authors.initials: R
authors.lastname: Benfeitas
authors.affiliation: Departament de Ciencies Mèdiques Bàsiques, Universitat de Lleida, Lleida, Spain.|Institut de Recerca Biomèdica de Lleida IRBLLeida, Edifici de Recerca Biomédica I, Av Rovira Roure 80, Lleida, Catalunya, 25198, Spain.
authors.forename: Ester
authors.initials: E
authors.lastname: Vilaprinyo
authors.affiliation: Departament de Ciencies Mèdiques Bàsiques, Universitat de Lleida, Lleida, Spain.|Institut de Recerca Biomèdica de Lleida IRBLLeida, Edifici de Recerca Biomédica I, Av Rovira Roure 80, Lleida, Catalunya, 25198, Spain.
authors.forename: Albert
authors.initials: A
authors.lastname: Sorribas
authors.affiliation: Computer Science Department and INSPIRES, University of Lleida, Jaume II 69, Lleida, Catalunya, 25001, Spain.
authors.forename: Francesc
authors.initials: F
authors.lastname: Solsona
authors.affiliation: Department of Plant Production and Forestry Science, School of Agrifood and Forestry Science and Engineering (ETSEA), University of Lleida Agrotecnio Center, Avenida Alcalde Rovira Roure 191, Lleida, 25198, Spain.
authors.forename: Gemma
authors.initials: G
authors.lastname: Farré
authors.affiliation: Department of Plant Production and Forestry Science, School of Agrifood and Forestry Science and Engineering (ETSEA), University of Lleida Agrotecnio Center, Avenida Alcalde Rovira Roure 191, Lleida, 25198, Spain.
authors.forename: Judit
authors.initials: J
authors.lastname: Berman
authors.affiliation: Department of Plant Production and Forestry Science, School of Agrifood and Forestry Science and Engineering (ETSEA), University of Lleida Agrotecnio Center, Avenida Alcalde Rovira Roure 191, Lleida, 25198, Spain.
authors.forename: Uxue
authors.initials: U
authors.lastname: Zorrilla
authors.affiliation: Department of Plant Production and Forestry Science, School of Agrifood and Forestry Science and Engineering (ETSEA), University of Lleida Agrotecnio Center, Avenida Alcalde Rovira Roure 191, Lleida, 25198, Spain.
authors.forename: Teresa
authors.initials: T
authors.lastname: Capell
authors.affiliation: Institute of Molecular Bioscience, J. W. Goethe University, Max von Laue Strasse 9, Frankfurt am Main, D-60438, Germany.
authors.forename: Gerhard
authors.initials: G
authors.lastname: Sandmann
authors.affiliation: Department of Plant Production and Forestry Science, School of Agrifood and Forestry Science and Engineering (ETSEA), University of Lleida Agrotecnio Center, Avenida Alcalde Rovira Roure 191, Lleida, 25198, Spain.
authors.forename: Changfu
authors.initials: C
authors.lastname: Zhu
authors.affiliation: Department of Plant Production and Forestry Science, School of Agrifood and Forestry Science and Engineering (ETSEA), University of Lleida Agrotecnio Center, Avenida Alcalde Rovira Roure 191, Lleida, 25198, Spain.|ICREA, Institució Catalana de Recerca i Estudis Avancats, Passeig Lluís Companys, 23, 08010, Barcelona, Spain.
authors.forename: Paul
authors.initials: P
authors.lastname: Christou
authors.affiliation: Departament de Ciencies Mèdiques Bàsiques, Universitat de Lleida, Lleida, Spain. ralves@cmb.udl.cat.|Institut de Recerca Biomèdica de Lleida IRBLLeida, Edifici de Recerca Biomédica I, Av Rovira Roure 80, Lleida, Catalunya, 25198, Spain. ralves@cmb.udl.cat.
authors.forename: Rui
authors.initials: R
authors.lastname: Alves
mesh_terms: D002338:Carotenoids / Q000378:metabolism*; D019295:Computational Biology / Q000379:methods; D055432:Metabolomics / Q000379:methods; D008962:Models, Theoretical; D003313:Zea mays / Q000378:metabolism*
chemical_list: D002338:Carotenoids
keywords: Zea mays; computational biology; mathematical modeling; metabolomics; synthetic biology; systems biology