K-Ath - Towards a Multi-Tissue Kinetic Model of Arabidopsis thaliana

k-ath - Towards a Multi-tissue Kinetic Model of Arabidopsis thaliana

Wheaton Schroeder and Rajib Saha

The University of Nebraska – Lincoln, Lincoln, NE

Arabidopsis thaliana has been a model system for modern plant science for the past three decades due to its small genome, short lifecycle, and ease of genetic manipulation. Its prominent role in omics and plant science research makes it an ideal choice for the creation and integration of emerging omics-based tools, including metabolic modeling of metabolism. Such computational modeling of metabolism is now an indispensable tool to drive the processes of understanding, discovering, and redesigning of any biological systems. Although Flux Balance Analysis (FBA) is the primary tool used for this purpose, it has significant limitations due to the lack of reaction kinetics, chemical species concentration, and metabolic regulation. These are critical to the understanding and subsequent design of engineering interventions directed to overproduction of specific bioproducts or improvement of plant performance, particularly in the presence of feedback regulation. Several metabolic models for A. thaliana already exist, and most regulatory interactions are well studied and documented. In addition, omics data is widely available for A. taliana as a model plant system including genomics, fluxomics, transcriptomics, and metabolomics. Hence, combining and advancing this knowledge in a kinetic model framework will allow us to study the interactions among biosynthesis pathways and individual tissue-types, thus proposing the in silico design of useful engineering interventions for A. thaliana. Moreover, this research will showcase the value of a plant-scale kinetic model for answering these questions in other plant species.

In this work, we are developing a plant-scale core metabolic network including such pathways as starch and sucrose metabolism; glycolysis and gluconeogenesis; citrate cycle; all amino acid biosynthesis pathways; pyruvate metabolism; the pentose phosphate pathway; photosynthesis and photorespiration pathways; and various transport and uptake pathways. At present, we have completed the draft development of three tissue-specific metabolic models: leaf (282 genes, 109 metabolites, and 191 reactions), seed (274 genes, 153 metabolites, and 222 reactions), and stem (12 genes, 54 metabolites, and 91 reactions). Moving forward, we will develop a root metabolic model, combine these four models in a plant-scale metabolic model, and using fluxomic, metabolomics, and transcriptomic data we will develop kinetic equation form for each reaction. Note that these metabolic models are restricted to core primary metabolism mainly due to the high computational requirements of the kinetic model framework. By decomposing each reaction to mass action kinetics, the rate constants for each mass action step will be determined with respect to fluxomic data, allowing us to solve for the kinetic constants of each kinetic equation in the system. Future work for this project includes sub-dividing existing tissue models, such as stem into xylem and phloem, and adding additional tissue types. Finally, this kinetic modeling framework of a model plant is transferable to other plant systems (provided the omics datasets are available for that species) to provide in silico design of useful engineering interventions.