The genome-scale metabolic model iIN800 of Saccharomyces cerevisiae and its validation: a scaffold to query lipid metabolism.
BACKGROUND
Up to now, there have been three published versions of a yeast genome-scale metabolic model: iFF708, iND750 and iLL672. All three models, however, lack a detailed description of lipid metabolism and thus are unable to be used as integrated scaffolds for gaining insights into lipid metabolism from multilevel omic measurement technologies (e.g. genome-wide mRNA levels). To overcome this limitation, we reconstructed a new version of the Saccharomyces cerevisiae genome-scale model, iIN800 that includes a more rigorous and detailed description of lipid metabolism.


RESULTS
The reconstructed metabolic model comprises 1446 reactions and 1013 metabolites. Beyond incorporating new reactions involved in lipid metabolism, we also present new biomass equations that improve the predictive power of flux balance analysis simulations. Predictions of both growth capability and large scale in silico single gene deletions by iIN800 were consistent with experimental data. In addition, 13C-labeling experiments validated the new biomass equations and calculated intracellular fluxes. To demonstrate the applicability of iIN800, we show that the model can be used as a scaffold to reveal the regulatory importance of lipid metabolism precursors and intermediates that would have been missed in previous models from transcriptome datasets.


CONCLUSIONS
Performing integrated analyses using iIN800 as a network scaffold is shown to be a valuable tool for elucidating the behavior of complex metabolic networks, particularly for identifying regulatory targets in lipid metabolism that can be used for industrial applications or for understanding lipid disease states.
Nookaew
Intawat
I
Department of Chemical Engineering, Faculty of Engineering, King Mongkut's University of Technology Thonburi, Bangkok 10140, Thailand. intawat.in@gmail.com
Jewett
Michael C
MC
Meechai
Asawin
A
Thammarongtham
Chinae
C
Laoteng
Kobkul
K
Cheevadhanarak
Supapon
S
Nielsen
Jens
J
Bhumiratana
Sakarindr
S
D018533:Biomass; D017353:Gene Deletion; D020869:Gene Expression Profiling; D016681:Genome, Fungal / Q000235:genetics*; D050356:Lipid Metabolism; D016366:Open Reading Frames; D012343:RNA, Transfer / Q000096:biosynthesis; D015203:Reproducibility of Results; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism*
D012343:RNA, Transfer