Development of a kinetic model of the phenylpropanoid pathway in potato tuber. Step 1: The construction of a comprehensive knowledge base

FERNANDO VILLARREAL; LANTERI, MARÍA LUCIANA; VALIÑAS, MATÍAS ARIEL; ANDREU, ADRIANA BALBINA; ARJEN TEN HAVE

Mar del Plata

Congreso; Noveno Congreso Argentino de Bioinformática y Biología Computacional; 2018

A2B2C

Background: Potato (Solanum tuberosum L.) constitutes a staple food at national and worldwide levels. Eventhough it has remarkable nutritional properties, commercial potato varieties present low contents of flavonoidsand anthocyanins, antioxidants that show impact in the prevention, treatment, and management of chronicdisease. However, potato andean varieties present higher levels of these compounds. The metabolicpathways leading to the biosynthesis of phenylpropanoids, including flavonoids and anthocyanins, form acomplex network that includes (i) reactions with substrates leading to (or converging from) multiple sub-pathways; (ii) promiscuous enzymes; and (iii) multiple isozymes that derive from gene superfamilies oralternative splicing. This hinders with breeding strategies to produce commercial varieties with higherflavonoid and anthocyanin contents.Objectives: A kinetic model for this pathway can be used to make quantitative predictions regarding the majorand minor metabolic flows. Such predictions could identify gene targets to alter the contents of specificcompounds, while having a minimal impact on other metabolites and pathways. Here, we present the first steprequired to construct such a model: the development of a knowledge database specific for potato tuber,containing comprehensive information of all known reactions, metabolites and genes involved in thebiosynthesis of phenylpropanoids.Results: Using public databases (KEGG, MetaCyc, ExplorEnz), we developed a first version of the metabolicpathway, written in SBGN using PathVisio. This was expanded based on metabolites reported to be detectedin tubers, according to data generated in our lab or from the literature (e.g., coumarins, modifiedanthocyanidins, isorhamnetin). Then, all the reactions were completed according to reactants, stoichiometry,and enzymes involved. Using databases (BRENDA, Uniprot, GenBank) and literature, we identified (wheneverpossible) genes with experimentally characterized activities. These genes were used to find potentialhomologous in potato. Finally, these candidates were filtered for expression in tubers of different varieties,using publicly available RNA-seq data. The final model was written using SBML in CellDesigner. Theknowledge base includes 202 reactions, 215 metabolites and 91 enzymes, with more than 300 tuber-specificcandidate genes.Conclusion: The knowledge-base is the pillar for the construction of a predictive kinetic model ofphenylpropanoid metabolism in potato tuber.