Metabolic network driven analysis of genome-wide transcription data from Aspergillus nidulans
Helga David1, Gerald Hofmann2, Ana Paula Oliveira2, Hanne Jarmer3 and Jens Nielsen2
1Fluxome Sciences A/S, Diplomvej, DK-2800 Kgs, Lyngby, Denmark
2Center for Microbial Biotechnology, BioCentrum-DTU, Technical University of Denmark, Søltofts Plads, DK-2800 Kgs, Lyngby, Denmark
3Center for Biological Sequence Analysis, BioCentrum-DTU, Technical University of Denmark, Kemitorvet, DK-2800 Kgs, Lyngby, Denmark
Aspergillus nidulans (the asexual form of Emericella nidulans) is a model organism for aspergilli, which are an important group of filamentous fungi that encompasses human and plant pathogens as well as industrial cell factories. Aspergilli have a highly diversified metabolism and, because of their medical, agricultural and biotechnological importance, it would be valuable to have an understanding of how their metabolism is regulated. We therefore conducted a genome-wide transcription analysis of A. nidulans grown on three different carbon sources (glucose, glycerol, and ethanol) with the objective of identifying global regulatory structures. Furthermore, we reconstructed the complete metabolic network of this organism, which resulted in linking 666 genes to metabolic functions, as well as assigning metabolic roles to 472 genes that were previously uncharacterized.
Through combination of the reconstructed metabolic network and the transcription data, we identified subnetwork structures that pointed to coordinated regulation of genes that are involved in many different parts of the metabolism. Thus, for a shift from glucose to ethanol, we identified coordinated regulation of the complete pathway for oxidation of ethanol, as well as upregulation of gluconeogenesis and downregulation of glycolysis and the pentose phosphate pathway. Furthermore, on change in carbon source from glucose to ethanol, the cells shift from using the pentose phosphate pathway as the major source of NADPH (nicotinamide adenine dinucleotide phosphatase, reduced form) for biosynthesis to use of the malic enzyme.
Our analysis indicates that some of the genes are regulated by common transcription factors, making it possible to establish new putative links between known transcription factors and genes through clustering.
Genome Biology 2006, 7:R108. This is an open access article distributed under the terms of the Creative Commons Attribution License.