Are we ready for genome-scale modeling in plants?

As it is becoming easier and faster to generate various types of high-throughput data, one would expect that by now we should have a comprehensive systems-level understanding of biology, biochemistry, and physiology at least in major prokaryotic and eukaryotic model systems. Despite the wealth of available data, we only get a glimpse of what is going on at the molecular level from the global perspective. The major reason is the high level of cellular complexity and our limited ability to identify all (or at least important) components and their interactions in virtually infinite number of internal and external conditions. Metabolism can be modeled mathematically by the use of genome-scale models (GEMs). GEMs are in silica metabolic flux models derived from available genome annotation. These models predict the combination of flux values of a defined metabolic network given the influence of internal and external signals. GEMs have been successfully implemented to model bacterial metabolism for over a decade. However, it was not until 2009 when the first GEM for Arabidopsis thaliana cell-suspension cultures was generated. Genome-scale modeling (GEMing) in plants brings new challenges primarily due to the missing components and complexity of plant cells represented by the existence of: (i) photosynthesis; (ii) compartmentation; (iii) variety of cell and tissue types; and (iv) diverse metabolic responses to environmental and developmental cues as well as pathogens, insects, and competing weeds. This review presents a critical discussion of the advantages of existing plant GEMs, while identifies key targets for future improvements. Plant GEMs tend to be accurate in predicting qualitative changes in selected aspects of central carbon metabolism, while secondary metabolism is largely neglected mainly due to the missing (unknown) genes and metabolites. As such, these models are suitable for exploring metabolism in plants grown in favorable conditions, but not in field-grown plants that have to cope with environmental changes in complex ecosystems. AraGEM is the first GEM describing a photosynthetic and photorespiring plant cell (Arabidopsis thaliana). We demonstrate the use of AraGEM given the current (limited) knowledge of plant metabolism and reveal the unexpected robustness of AraGEM by a series of in silico simulations. The major focus of these simulations is on the assessment of the: (i) network connectivity; (ii) influence of CO2 and photon uptake rates on cellular growth rates and production of individual biomass components; and (iii) stability of plant central carbon metabolism with internal pH changes. (C) 2012 Elsevier Ireland Ltd. All rights reserved.