The previous chapter described the procedures developed for studying the systems biology of metabolism in bacteria. In parallel, similar efforts have been undertaken for unicellular eukaryotes. The main challenge that arises is the presence of multiple intracellular compartments (organelles), that, in principle, can be dealt with during a reconstruction process, but in practice is difficult due to the scarcity of data of transporters that move metabolites in and out of organelles. The yeast Saccharomyces cerevisiae was the first eukaryote to undergo a genome-scale metabolic reconstruction in 2003. This achievement was followed by the reconstruction of other fungal species. A detailed reconstruction of photosynthetic green algae appeared in 2011. Reconstruction of metabolic networks in multicellular organisms have also appeared. The first version of the genome-scale human metabolic map was published in 2007, followed by parallel reconstruction efforts for other mammals. This global human map has since been customized for various cell and tissue types. Interacting models of multiple tissue types have appeared that, in principle, should be able to study systemic metabolism in humans. Therefore, it appears that the network reconstruction procedures that have developed for E. coli will extend to multicellular organisms; however, no model of metabolism in the elephant has yet appeared.

Metabolism in Saccharomyces cerevisiae

6.1.1 Reconstruction and its uses

Besides being an industrial workhorse for a variety of biotechnological products, S. cerevisiae (baker's yeast) is a well-developed model organism for biochemical, genetic, pharmacological, and post-genomic studies. Several attempts at reconstructing its metabolic network from genomic and literature data have been made, as summarized in Figure 6.1.

History Shortly after the first pre-genome era E. coli models were published, a similar effort was undertaken for yeast. This undertaking is more difficult than for E. coli because the organism is more complicated, and unlike for E. coli, much of the yeast literature is genetic in nature and contains less detailed biochemistry.