Regulation of the Aldehyde Dehydrogenase Gene (aldA) and Its Role in the Control of the Coinducer Level Necessary for Induction of the Ethanol Utilization Pathway in Aspergillus nidulans

• DOI: 10.1074/jbc.m005769200
• Publication Date: 2002-07-26T15:09:37Z
• Authors: Michel Flipphi; Martine Mathieu; Irina Cirpus; Cristina Panozzo; Béatrice Felenbok
• Keywords: Transcriptional Activation; 0303 health sciences; Binding Sites; Ethanol; Models, Genetic; Transcription, Genetic; Molecular Sequence Data; Alcohol Dehydrogenase; Aldehyde Dehydrogenase; Models, Biological; Aspergillus nidulans; Gene Expression Regulation, Enzymologic; Fungal Proteins; Repressor Proteins; 03 medical and health sciences; Enhancer Elements, Genetic; Transduction, Genetic; Mutation; RNA; Promoter Regions, Genetic; Alleles; Cell Division

Expression of the structural genes for alcohol and aldehyde dehydrogenase, alcA and aldA, respectively, enables the fungus Aspergillus nidulans to grow on ethanol. The pathway-specific transcriptional activator AlcR mediates the induction of ethanol catabolism in the presence of a coinducing compound. Ethanol catabolism is further subject to negative control mediated by the general carbon catabolite repressor CreA. Here we show that, in contrast to alcA and alcR, the aldA gene is not directly subject to CreA repression. A single cis-acting element mediates AlcR activation of aldA. Furthermore, we show that the induction of the alc gene system is linked to in situ aldehyde dehydrogenase activity. In aldA loss-of-function mutants, the alc genes are induced under normally noninducing conditions. This pseudo-constitutive expression correlates with the nature of the mutations, suggesting that this feature is caused by an intracellular accumulation of a coinducing compound. Conversely, constitutive overexpression of aldA results in suppression of induction in the presence of ethanol. This shows unambiguously that acetaldehyde is the sole physiological inducer of ethanol catabolism. We hypothesize that the intracellular acetaldehyde concentration is the critical factor governing the induction of the alc gene system.