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Originally published In Press as doi:10.1074/jbc.M005769200 on December 1, 2000

J. Biol. Chem., Vol. 276, Issue 10, 6950-6958, March 9, 2001
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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*

Michel FlipphiDagger , Martine MathieuDagger , Irina Cirpus§, Cristina Panozzo, and Béatrice FelenbokDagger ||

From the Dagger  Institut de Génétique et Microbiologie, CNRS UMR 8621, Université Paris-Sud XI, Centre Universitaire d'Orsay, Bâtiment 409, F-91405 Orsay Cedex, France

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.


* This work was supported in part by CNRS Grant UMR 8621, the Université Paris-Sud XI, and from the European Community Contracts BIO4-CT96-0535 and QLCK3-CT1999-00729.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The nucleotide sequence(s) reported in this paper has been submitted to the GenBankTM/EMBL Data Bank with accession number(s) AF260123, AF260124, AF260125, and AF260126.

§ Supported by the Erasmus student exchange program. Present address: Fachbereich Biologie, Philipps-Universität Marburg, Karl-von Frischstrasse, D-35032 Marburg, Germany.

Present address: Laboratoire de Neurogénétique Moléculaire, E. 9913, GENOPOLE, 2 Rue Gaston Crémieux, CP5724, F-91057 Evry Cedex, France.

|| To whom correspondence should be addressed. Tel.: 33 1 69156328; Fax: 33 1 69157808; E-mail: felenbok@igmors.u-psud.fr.


Copyright © 2001 by The American Society for Biochemistry and Molecular Biology, Inc.


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