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

Abstract

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, thealdA gene is not directly subject to CreA repression. A single cis-acting element mediates AlcR activation ofaldA. Furthermore, we show that the induction of thealc 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.AF260123AF260124AF260125AF260126 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, thealdA gene is not directly subject to CreA repression. A single cis-acting element mediates AlcR activation ofaldA. Furthermore, we show that the induction of thealc 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.AF260123AF260124AF260125AF260126 alcohol dehydrogenase I alcohol dehydrogenase aldehyde dehydrogenase ethylmethyl ketone (2-butanone) kilobase pair base pair The fungal model organism, Aspergillus nidulans, is able to grow on ethanol as the sole source of carbon (1Felenbok B. Sealy-Lewis H.M. Prog. Ind. Microbiol. 1994; 29: 141-179PubMed Google Scholar, 2Felenbok B. Kelly J.M. Brambl R. Marzluf G. The Mycota III: Biochemistry and Molecular Biology. Springer-Verlag, Berlin1996: 369-380Google Scholar). Alcohol is oxidized via acetaldehyde into acetate, which enters mainstream metabolism in its activated form, acetyl-CoA. The two enzymes responsible for acetate formation, i.e. alcohol dehydrogenase I (ADHI)1 (EC1.1.1.1) and aldehyde dehydrogenase (ALDH) (EC 1.2.1.5), are encoded by the unlinked alcA and aldA genes, respectively. Ethanol catabolism is inducible by a variety of compounds and is driven by the irreversible conversion of acetaldehyde into acetate.Induction of ethanol catabolism further requires the action of a pathway-specific DNA-binding activator protein, AlcR, regulating both structural genes at the level of transcription (3Pateman J.A. Doy C.R. Olsen J.E. Norris U. Creaser E.H. Hynes M. Proc. R. Soc. Lond. Ser. B Biol. Sci. 1983; 217: 243-264Crossref PubMed Scopus (76) Google Scholar, 4Lockington R.A. Sealy-Lewis H.M. Scazzocchio C. Davies R.W. Gene ( Amst. ). 1985; 33: 137-149Crossref PubMed Scopus (108) Google Scholar, 5Lockington R. Scazzocchio C. Sequeval D. Mathieu M. Felenbok B. Mol. Microbiol. 1987; 1: 275-281Crossref PubMed Scopus (56) Google Scholar, 6Kulmburg P. Sequeval D. Lenouvel F. Mathieu M. Felenbok B. Mol. Cell. Biol. 1992; 12: 1932-1939Crossref PubMed Scopus (48) Google Scholar, 7Mathieu M. Felenbok B. EMBO J. 1994; 13: 4022-4027Crossref PubMed Scopus (115) Google Scholar). The encodingalcR gene, closely linked to alcA, concomitantly activates its own transcription. This autoactivation enables the adaptation toward ethanol conversion upon induction. Moreover, thealcR activation cascade mechanism a alcA and aldA are the inducible fungal genes to (1Felenbok B. Sealy-Lewis H.M. Prog. Ind. Microbiol. 1994; 29: 141-179PubMed Google Scholar, B. J. PubMed Scopus Google of carbon induced ethanol catabolism This as carbon catabolite is mediated at the level of transcription via a DNA-binding protein, CreA B. Kelly J.M. Brambl R. Marzluf G. The Mycota III: Biochemistry and Molecular Biology. Springer-Verlag, Berlin1996: 369-380Google Scholar, P. Mathieu M. C. Kelly J. Felenbok B. Mol. Microbiol. PubMed Scopus Google Scholar). this negative control is are subject to carbon catabolite by of the CreA CreA to directly on both the structural and the gene, a and of ethanol conversion under M. Felenbok B. EMBO J. 1994; 13: 4022-4027Crossref PubMed Scopus (115) Google Scholar, P. Mathieu M. C. Kelly J. Felenbok B. Mol. Microbiol. PubMed Scopus Google Scholar, M. Felenbok B. Mol. Microbiol. PubMed Scopus Google Scholar). In the presence of both and the inducer the is that the induction of genes for ethanol the two control a of the expression and alcA a to C. Mathieu M. Felenbok B. PubMed Scopus Google Scholar). A of the of the ethanol in in the we the in for activation and in the structural alcA gene C. Felenbok B. J. Biol. PubMed Scopus Google C. Felenbok B. J. Biol. PubMed Scopus Google and the gene M. Felenbok B. EMBO J. 1994; 13: 4022-4027Crossref PubMed Scopus (115) Google Scholar, M. Felenbok B. Mol. Microbiol. PubMed Scopus Google Scholar). In both genes cis-acting AlcR in alcA to upon transcriptional which the of the alcA upon a single activation Furthermore, and induction to at the level to a the two DNA-binding as cis-acting in both the alcA and in In we for the of a of action by which CreA transcriptional of the this we the by which the two control on the transcriptional induction of the structural aldA aldA and at the level R.A. Sealy-Lewis H.M. Scazzocchio C. Davies R.W. Gene ( Amst. ). 1985; 33: 137-149Crossref PubMed Scopus (108) Google Scholar, M. R. Davies R.W. R.A. Scazzocchio C. Sealy-Lewis H.M. Gene ( Amst. ). 1987; PubMed Scopus Google Scholar, Davies R.W. R.A. Scazzocchio C. Sealy-Lewis H.M. Gene ( Amst. ). 1987; PubMed Scopus Google Scholar). that at the the transcription that of the two genes of ethanol control of aldA expression the for a coinducing compound. is that acetaldehyde i.e. is to acetate J. PubMed Scopus Google Scholar). This irreversible conversion ethanol catabolism E.H. J.A. J. 1987; Scopus Google Scholar). Moreover, acetaldehyde is the to and induction of the alc gene system (1Felenbok B. Sealy-Lewis H.M. Prog. Ind. Microbiol. 1994; 29: 141-179PubMed Google Scholar, J.A. Doy C.R. Olsen J.E. Norris U. Creaser E.H. Hynes M. Proc. R. Soc. Lond. Ser. B Biol. Sci. 1983; 217: 243-264Crossref PubMed Scopus (76) Google Scholar, 5Lockington R. Scazzocchio C. Sequeval D. Mathieu M. Felenbok B. Mol. Microbiol. 1987; 1: 275-281Crossref PubMed Scopus (56) Google Scholar, J. Google B. Sequeval D. Mathieu M. Davies R.W. Gene ( Amst. ). PubMed Scopus (56) Google Scholar). The of in that the expression of the aldA gene is to subject to ethanol and acetaldehyde as physiological of the system (3Pateman J.A. Doy C.R. Olsen J.E. Norris U. Creaser E.H. Hynes M. Proc. R. Soc. Lond. Ser. B Biol. Sci. 1983; 217: 243-264Crossref PubMed Scopus (76) Google Scholar, H.M. R.A. PubMed Scopus Google Scholar). of the of the physiological inducer not to the of the in the induction we the expression of the induction of the This to the of the physiological inducer with to ethanol catabolism. Furthermore, we that a control and alcA gene expression is for the and of an this we the of the pathway-specific AlcR and a coinducing for the transcriptional induction of the nidulans aldA gene structural gene aldehyde We that in for of the of of the aldA We that the sole the activation of transcription by AlcR activation in P. Sequeval D. Lenouvel F. Mathieu M. Felenbok B. Mol. Cell. Biol. 1992; 12: 1932-1939Crossref PubMed Scopus (48) Google Scholar, M. Felenbok B. Mol. Microbiol. PubMed Scopus Google Scholar, C. Felenbok B. J. Biol. PubMed Scopus Google of two AlcR The in aldA is as an of both with an A at the Lenouvel F. Felenbok B. Mol. Microbiol. PubMed Scopus Google Scholar). Furthermore, by a a gene, we that aldA is not subject to by of the general carbon catabolite repressor CreA. the structural gene for ethanol of the for aldA transcriptional repression. The sole CreA thealdA the single AlcR is not to subject to carbon catabolite repression. CreA in nidulans to of two CreA M. Felenbok B. Mol. Microbiol. PubMed Scopus Google Scholar, C. Felenbok B. J. Biol. PubMed Scopus Google Scholar, B. Scazzocchio C. EMBO J. 1994; 13: PubMed Scopus Google Scholar, J. J. Mol. Microbiol. PubMed Scopus Google the by which the two control pathway-specific induction and general carbon catabolite on the genes of ethanol catabolism In both and aldA, activation is mediated via a single AlcR in alcA are The in alcA to in C. Felenbok B. J. Biol. PubMed Scopus Google and this for the of the upon induction of the alc gene thealdA at as as that of alcA, the that activation The of the CreA repressor in the expression of alcA and that that the repressor and activator for on the in both genes under C. Mathieu M. Felenbok B. PubMed Scopus Google Scholar). catabolite is a that on the carbon source In carbon catabolite is a of CreA in both thealcR and alcA genes not to a in the presence of results in overexpression under induced M. Felenbok B. EMBO J. 1994; 13: 4022-4027Crossref PubMed Scopus (115) Google Scholar, M. Felenbok B. Mol. Microbiol. PubMed Scopus Google Scholar, C. Felenbok B. J. Biol. PubMed Scopus Google Scholar). transcription is in a the aldA is subject to The expression of aldA the of the AlcR activation cascade mechanism mediated via a single cis-acting the in on the and the in which the AlcR that the the two of a as as of the AlcR in F. Felenbok B. J. Biol. PubMed Scopus Google Scholar, Lenouvel F. Felenbok B. Mol. Microbiol. PubMed Scopus Google Scholar). that in AlcR, the AlcR is not in in transcriptional The for the transcription of aldA in the of of AlcR to the this is Lenouvel F. Felenbok B. Mol. Microbiol. PubMed Scopus Google Scholar). is the the activation and the the transcription the aldA to the general transcription that in nidulans in to an induction R. J. F. Scazzocchio C. EMBO J. PubMed Scopus Google Scholar). the of in the of a not in this is that acetaldehyde is the physiological inducer of ethanol in with the aldA that acetaldehyde metabolism under noninducing is not into acetate, the alc gene system is induced In the aldA the expression level of and aldA in the of thealdA i.e. the accumulation of with we that acetaldehyde induction to and B. Ethanol an of a induced by a and not by the is to Scopus Google Scholar, R. G. PubMed Scopus Google Scholar). results a the the and the of this grow on carbon the of activity. the acetaldehyde in this by by to by that is to an for in by is by E.H. J.A. Doy J. 1985; PubMed Scopus Google Scholar). to that of as the presence of that not by to on ethanol. In the presence of ethanol as the sole carbon of the of acetaldehyde the is toward of ethanol. of the of pseudo-constitutive expression is the presence of a A induction of alcA in the of the induction accumulation of acetaldehyde to an ethanol. the in intracellular the activation system the expression of the genes a acetaldehyde concentration the is The presence of AlcR in with in the AlcR in alcA, to a in to of In of we that the AlcR in the alcA are in transcriptional activation C. Felenbok B. J. Biol. PubMed Scopus Google Scholar). we that mutants, a gene which is not subject to autoactivation to the of the AlcR are able to grow on ethanol as the sole carbon source M. Felenbok B. Mol. Microbiol. PubMed Scopus Google the induction of the genes is that in the This the of the gene into The adaptation in to not induced expression is by its the of acetaldehyde as the the of induction. requires acetaldehyde requires expression of requires induction of alcA by AlcR via induction of alcA, a constitutive level expression of the gene is and transcription is and is in loss-of-function M. Felenbok B. EMBO J. 1994; 13: 4022-4027Crossref PubMed Scopus (115) Google Scholar, M. Felenbok B. Mol. Microbiol. PubMed Scopus Google Scholar, C. Mathieu M. Felenbok B. PubMed Scopus Google Scholar, Lenouvel F. Felenbok B. J. Biol. PubMed Scopus Google Scholar). the of the induction the level of acetaldehyde further the conversion of the in acetaldehyde concentration are in the and of the induction is by the constitutive expression of aldA in the of as is the in the of intracellular a the induction is to a to This that the in situ level of an in the of the to the transcriptional activator control of both aldA and alcA gene in to intracellular of for the and of an ethanol. The fungal model organism, Aspergillus nidulans, is able to grow on ethanol as the sole source of carbon (1Felenbok B. Sealy-Lewis H.M. Prog. Ind. Microbiol. 1994; 29: 141-179PubMed Google Scholar, 2Felenbok B. Kelly J.M. Brambl R. Marzluf G. The Mycota III: Biochemistry and Molecular Biology. Springer-Verlag, Berlin1996: 369-380Google Scholar). Alcohol is oxidized via acetaldehyde into acetate, which enters mainstream metabolism in its activated form, acetyl-CoA. The two enzymes responsible for acetate formation, i.e. alcohol dehydrogenase I (ADHI)1 (EC1.1.1.1) and aldehyde dehydrogenase (ALDH) (EC 1.2.1.5), are encoded by the unlinked alcA and aldA genes, respectively. Ethanol catabolism is inducible by a variety of compounds and is driven by the irreversible conversion of acetaldehyde into of ethanol catabolism further requires the action of a pathway-specific DNA-binding activator protein, AlcR, regulating both structural genes at the level of transcription (3Pateman J.A. Doy C.R. Olsen J.E. Norris U. Creaser E.H. Hynes M. Proc. R. Soc. Lond. Ser. B Biol. Sci. 1983; 217: 243-264Crossref PubMed Scopus (76) Google Scholar, 4Lockington R.A. Sealy-Lewis H.M. Scazzocchio C. Davies R.W. Gene ( Amst. ). 1985; 33: 137-149Crossref PubMed Scopus (108) Google Scholar, 5Lockington R. Scazzocchio C. Sequeval D. Mathieu M. Felenbok B. Mol. Microbiol. 1987; 1: 275-281Crossref PubMed Scopus (56) Google Scholar, 6Kulmburg P. Sequeval D. Lenouvel F. Mathieu M. Felenbok B. Mol. Cell. Biol. 1992; 12: 1932-1939Crossref PubMed Scopus (48) Google Scholar, 7Mathieu M. Felenbok B. EMBO J. 1994; 13: 4022-4027Crossref PubMed Scopus (115) Google Scholar). The encodingalcR gene, closely linked to alcA, concomitantly activates its own transcription. This autoactivation enables the adaptation toward ethanol conversion upon induction. Moreover, thealcR activation cascade mechanism a alcA and aldA are the inducible fungal genes to (1Felenbok B. Sealy-Lewis H.M. Prog. Ind. Microbiol. 1994; 29: 141-179PubMed Google Scholar, B. J. PubMed Scopus Google Scholar). of carbon induced ethanol catabolism This as carbon catabolite is mediated at the level of transcription via a DNA-binding protein, CreA B. Kelly J.M. Brambl R. Marzluf G. The Mycota III: Biochemistry and Molecular Biology. Springer-Verlag, Berlin1996: 369-380Google Scholar, P. Mathieu M. C. Kelly J. Felenbok B. Mol. Microbiol. PubMed Scopus Google Scholar). this negative control is are subject to carbon catabolite by of the CreA CreA to directly on both the structural and the gene, a and of ethanol conversion under M. Felenbok B. EMBO J. 1994; 13: 4022-4027Crossref PubMed Scopus (115) Google Scholar, P. Mathieu M. C. Kelly J. Felenbok B. Mol. Microbiol. PubMed Scopus Google Scholar, M. Felenbok B. Mol. Microbiol. PubMed Scopus Google Scholar). In the presence of both and the inducer the is that the induction of genes for ethanol the two control a of the expression and alcA a to C. Mathieu M. Felenbok B. PubMed Scopus Google Scholar). A of the of the ethanol in in the we the in for activation and in the structural alcA gene C. Felenbok B. J. Biol. PubMed Scopus Google C. Felenbok B. J. Biol. PubMed Scopus Google and the gene M. Felenbok B. EMBO J. 1994; 13: 4022-4027Crossref PubMed Scopus (115) Google Scholar, M. Felenbok B. Mol. Microbiol. PubMed Scopus Google Scholar). In both genes cis-acting AlcR in alcA to upon transcriptional which the of the alcA upon a single activation Furthermore, and induction to at the level to a the two DNA-binding as cis-acting in both the alcA and in In we for the of a of action by which CreA transcriptional of the In this we the by which the two control on the transcriptional induction of the structural aldA aldA and at the level R.A. Sealy-Lewis H.M. Scazzocchio C. Davies R.W. Gene ( Amst. ). 1985; 33: 137-149Crossref PubMed Scopus (108) Google Scholar, M. R. Davies R.W. R.A. Scazzocchio C. Sealy-Lewis H.M. Gene ( Amst. ). 1987; PubMed Scopus Google Scholar, Davies R.W. R.A. Scazzocchio C. Sealy-Lewis H.M. Gene ( Amst. ). 1987; PubMed Scopus Google Scholar). that at the the transcription that of the two genes of ethanol catabolism. The control of aldA expression the for a coinducing compound. is that acetaldehyde i.e. is to acetate J. PubMed Scopus Google Scholar). This irreversible conversion ethanol catabolism E.H. J.A. J. 1987; Scopus Google Scholar). Moreover, acetaldehyde is the to and induction of the alc gene system (1Felenbok B. Sealy-Lewis H.M. Prog. Ind. Microbiol. 1994; 29: 141-179PubMed Google Scholar, J.A. Doy C.R. Olsen J.E. Norris U. Creaser E.H. Hynes M. Proc. R. Soc. Lond. Ser. B Biol. Sci. 1983; 217: 243-264Crossref PubMed Scopus (76) Google Scholar, 5Lockington R. Scazzocchio C. Sequeval D. Mathieu M. Felenbok B. Mol. Microbiol. 1987; 1: 275-281Crossref PubMed Scopus (56) Google Scholar, J. Google B. Sequeval D. Mathieu M. Davies R.W. Gene ( Amst. ). PubMed Scopus (56) Google Scholar). The of in that the expression of the aldA gene is to subject to ethanol and acetaldehyde as physiological of the system (3Pateman J.A. Doy C.R. Olsen J.E. Norris U. Creaser E.H. Hynes M. Proc. R. Soc. Lond. Ser. B Biol. Sci. 1983; 217: 243-264Crossref PubMed Scopus (76) Google Scholar, H.M. R.A. PubMed Scopus Google Scholar). of the of the physiological inducer not to the of the in the induction we the expression of the induction of the This to the of the physiological inducer with to ethanol catabolism. Furthermore, we that a control and alcA gene expression is for the and of an ethanol. this we the of the pathway-specific AlcR and a coinducing for the transcriptional induction of the nidulans aldA gene structural gene aldehyde We that in for of the of of the aldA We that the sole the activation of transcription by AlcR activation in P. Sequeval D. Lenouvel F. Mathieu M. Felenbok B. Mol. Cell. Biol. 1992; 12: 1932-1939Crossref PubMed Scopus (48) Google Scholar, M. Felenbok B. Mol. Microbiol. PubMed Scopus Google Scholar, C. Felenbok B. J. Biol. PubMed Scopus Google of two AlcR The in aldA is as an of both with an A at the Lenouvel F. Felenbok B. Mol. Microbiol. PubMed Scopus Google Scholar). Furthermore, by a a gene, we that aldA is not subject to by of the general carbon catabolite repressor CreA. the structural gene for ethanol of the for aldA transcriptional repression. The sole CreA thealdA the single AlcR is not to subject to carbon catabolite repression. CreA in nidulans to of two CreA M. Felenbok B. Mol. Microbiol. PubMed Scopus Google Scholar, C. Felenbok B. J. Biol. PubMed Scopus Google Scholar, B. Scazzocchio C. EMBO J. 1994; 13: PubMed Scopus Google Scholar, J. J. Mol. Microbiol. PubMed Scopus Google the by which the two control pathway-specific induction and general carbon catabolite on the genes of ethanol catabolism In both and aldA, activation is mediated via a single AlcR in alcA are The in alcA to in C. Felenbok B. J. Biol. PubMed Scopus Google and this for the of the upon induction of the alc gene thealdA at as as that of alcA, the that activation The of the CreA repressor in the expression of alcA and that that the repressor and activator for on the in both genes under C. Mathieu M. Felenbok B. PubMed Scopus Google Scholar). catabolite is a that on the carbon source In carbon catabolite is a of CreA in both thealcR and alcA genes not to a in the presence of results in overexpression under induced M. Felenbok B. EMBO J. 1994; 13: 4022-4027Crossref PubMed Scopus (115) Google Scholar, M. Felenbok B. Mol. Microbiol. PubMed Scopus Google Scholar, C. Felenbok B. J. Biol. PubMed Scopus Google Scholar). transcription is in a the aldA is subject to The expression of aldA the of the AlcR activation cascade mechanism mediated via a single cis-acting the in on the and the in which the AlcR that the the two of a as as of the AlcR in F. Felenbok B. J. Biol. PubMed Scopus Google Scholar, Lenouvel F. Felenbok B. Mol. Microbiol. PubMed Scopus Google Scholar). that in AlcR, the AlcR is not in in transcriptional The for the transcription of aldA in the of of AlcR to the this is Lenouvel F. Felenbok B. Mol. Microbiol. PubMed Scopus Google Scholar). is the the activation and the the transcription the aldA to the general transcription that in nidulans in to an induction R. J. F. Scazzocchio C. EMBO J. PubMed Scopus Google Scholar). the of in the of a not in this is that acetaldehyde is the physiological inducer of ethanol in with the aldA that acetaldehyde metabolism under noninducing is not into acetate, the alc gene system is induced In the aldA the expression level of and aldA in the of thealdA i.e. the accumulation of with we that acetaldehyde induction to and B. Ethanol an of a induced by a and not by the is to Scopus Google Scholar, R. G. PubMed Scopus Google Scholar). results a the the and the of this grow on carbon the of activity. the acetaldehyde in this by by to by that is to an for in by is by E.H. J.A. Doy J. 1985; PubMed Scopus Google Scholar). to that of as the presence of that not by to on ethanol. In the presence of ethanol as the sole carbon of the of acetaldehyde the is toward of ethanol. of the of pseudo-constitutive expression is the presence of a A induction of alcA in the of the induction accumulation of acetaldehyde to an ethanol. the in intracellular the activation system the expression of the genes a acetaldehyde concentration the is The presence of AlcR in with in the AlcR in alcA, to a in to of In of we that the AlcR in the alcA are in transcriptional activation C. Felenbok B. J. Biol. PubMed Scopus Google Scholar). we that mutants, a gene which is not subject to autoactivation to the of the AlcR are able to grow on ethanol as the sole carbon source M. Felenbok B. Mol. Microbiol. PubMed Scopus Google the induction of the genes is that in the This the of the gene into The adaptation in to not induced expression is by its the of acetaldehyde as the the of induction. requires acetaldehyde requires expression of requires induction of alcA by AlcR via induction of alcA, a constitutive level expression of the gene is and transcription is and is in loss-of-function M. Felenbok B. EMBO J. 1994; 13: 4022-4027Crossref PubMed Scopus (115) Google Scholar, M. Felenbok B. Mol. Microbiol. PubMed Scopus Google Scholar, C. Mathieu M. Felenbok B. PubMed Scopus Google Scholar, Lenouvel F. Felenbok B. J. Biol. PubMed Scopus Google Scholar). the of the induction the level of acetaldehyde further the conversion of the in acetaldehyde concentration are in the and of the induction is by the constitutive expression of aldA in the of as is the in the of intracellular a the induction is to a to This that the in situ level of an in the of the to the transcriptional activator control of both aldA and alcA gene in to intracellular of for the and of an ethanol. In this we the of the pathway-specific AlcR and a coinducing for the transcriptional induction of the nidulans aldA gene structural gene aldehyde We that in for of the of of the aldA We that the sole the activation of transcription by AlcR activation in P. Sequeval D. Lenouvel F. Mathieu M. Felenbok B. Mol. Cell. Biol. 1992; 12: 1932-1939Crossref PubMed Scopus (48) Google Scholar, M. Felenbok B. Mol. Microbiol. PubMed Scopus Google Scholar, C. Felenbok B. J. Biol. PubMed Scopus Google of two AlcR The in aldA is as an of both with an A at the Lenouvel F. Felenbok B. Mol. Microbiol. PubMed Scopus Google Scholar). Furthermore, by a a gene, we that aldA is not subject to by of the general carbon catabolite repressor CreA. the structural gene for ethanol of the for aldA transcriptional repression. The sole CreA thealdA the single AlcR is not to subject to carbon catabolite repression. CreA in nidulans to of two CreA M. Felenbok B. Mol. Microbiol. PubMed Scopus Google Scholar, C. Felenbok B. J. Biol. PubMed Scopus Google Scholar, B. Scazzocchio C. EMBO J. 1994; 13: PubMed Scopus Google Scholar, J. J. Mol. Microbiol. PubMed Scopus Google Scholar). We the by which the two control pathway-specific induction and general carbon catabolite on the genes of ethanol catabolism In both and aldA, activation is mediated via a single AlcR in alcA are The in alcA to in C. Felenbok B. J. Biol. PubMed Scopus Google and this for the of the upon induction of the alc gene thealdA at as as that of alcA, the that activation The of the CreA repressor in the expression of alcA and that that the repressor and activator for on the in both genes under C. Mathieu M. Felenbok B. PubMed Scopus Google Scholar). catabolite is a that on the carbon source In carbon catabolite is a of CreA in both thealcR and alcA genes not to a in the presence of results in overexpression under induced M. Felenbok B. EMBO J. 1994; 13: 4022-4027Crossref PubMed Scopus (115) Google Scholar, M. Felenbok B. Mol. Microbiol. PubMed Scopus Google Scholar, C. Felenbok B. J. Biol. PubMed Scopus Google Scholar). transcription is in a the aldA is subject to The expression of aldA the of the AlcR activation cascade mechanism mediated via a single cis-acting the in on the and the in which the AlcR that the the two of a as as of the AlcR in F. Felenbok B. J. Biol. PubMed Scopus Google Scholar, Lenouvel F. Felenbok B. Mol. Microbiol. PubMed Scopus Google Scholar). that in AlcR, the AlcR is not in in transcriptional The for the transcription of aldA in the of of AlcR to the this is Lenouvel F. Felenbok B. Mol. Microbiol. PubMed Scopus Google Scholar). is the the activation and the the transcription the aldA to the general transcription that in nidulans in to an induction R. J. F. Scazzocchio C. EMBO J. PubMed Scopus Google Scholar). the of in the of a not The in this is that acetaldehyde is the physiological inducer of ethanol in with the aldA that acetaldehyde metabolism under noninducing is not into acetate, the alc gene system is induced In the aldA the expression level of and aldA in the of thealdA i.e. the accumulation of with we that acetaldehyde induction to and B. Ethanol an of a induced by a and not by the is to Scopus Google Scholar, R. G. PubMed Scopus Google Scholar). results a the the and the of this grow on carbon the of activity. the acetaldehyde in this by by to by that is to an for in by is by E.H. J.A. Doy J. 1985; PubMed Scopus Google Scholar). to that of as the presence of that not by to on ethanol. In the presence of ethanol as the sole carbon of the of acetaldehyde the is toward of ethanol. of the of pseudo-constitutive expression is the presence of a A induction of alcA in the of the induction accumulation of acetaldehyde to an ethanol. the in intracellular the activation system the expression of the genes a acetaldehyde concentration the is The presence of AlcR in with in the AlcR in alcA, to a in to of In of we that the AlcR in the alcA are in transcriptional activation C. Felenbok B. J. Biol. PubMed Scopus Google Scholar). we that mutants, a gene which is not subject to autoactivation to the of the AlcR are able to grow on ethanol as the sole carbon source M. Felenbok B. Mol. Microbiol. PubMed Scopus Google the induction of the genes is that in the This the of the gene into The adaptation in to not induced expression is by its the of acetaldehyde as the the of induction. requires acetaldehyde requires expression of requires induction of alcA by AlcR via induction of alcA, a constitutive level expression of the gene is and transcription is and is in loss-of-function M. Felenbok B. EMBO J. 1994; 13: 4022-4027Crossref PubMed Scopus (115) Google Scholar, M. Felenbok B. Mol. Microbiol. PubMed Scopus Google Scholar, C. Mathieu M. Felenbok B. PubMed Scopus Google Scholar, Lenouvel F. Felenbok B. J. Biol. PubMed Scopus Google Scholar). the of the induction the level of acetaldehyde further the conversion of the in acetaldehyde concentration are in the and of the induction is by the constitutive expression of aldA in the of as is the in the of intracellular a the induction is to a to This that the in situ level of an in the of the to the transcriptional activator A control of both aldA and alcA gene in to intracellular of for the and of an ethanol. We and M. Sealy-Lewis with C. for and M. for the