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

author email corresponding author email

Genome Biology 2006, 7:R108doi:10.1186/gb-2006-7-11-r108


Published:	15 November 2006

Subject areas: Physiology, Microbiology and parasitology, Biochemistry and structural biology

Abstract

Background

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.

Results

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.

Conclusion

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.