Genome-scale reconstruction of Saccharomyces cerevisiae.
Natalie Duarte, Markus Herrgard, Bernhard Palsson
Bioengineering, Univ of California, San Diego, 9500 Gilman Dr, La Jolla, CA, 92037-0412, USA
High-throughput experimental technologies have led to the accumulation of genomic, transcriptomic, proteomic, and metabolomic data, and the integration of these various data types is central to enabling a systemic understanding of cellular functions. Genome-scale metabolic networks have been successfully reconstructed for several microorganisms, including Escherichia coli, Haemophilus influenzae, Helicobacter pylori, and Saccharomyces cerevisiae. As the most comprehensive model of a eukaryotic organism to date, the S. cerevisiae iND750 metabolic network is a prototypic example of the transition to genome-scale science. In this lecture, the reconstruction of this fully-compartmentalized network will be described as well as the systematic method in which we identified inconsistencies and gaps in our knowledge of yeast metabolism. Special attention will be focused on the importance of global proton balancing, the effects of pH, and the evaluation of evidence for each enzymatic and transport reaction. Finally, we will discuss our progress in integrating transcriptional regulation and signaling pathways into our metabolic network to produce a fully integrated single-cell model.
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