RESUMO
The ethanol utilization pathway in Aspergillus nidulans is a model system, which has been thoroughly elucidated at the biochemical, genetic and molecular levels. Three main elements are involved: (a) high level expression of the positively autoregulated activator AlcR; (b) the strong promoters of the structural genes for alcohol dehydrogenase (alcA) and aldehyde dehydrogenase (aldA); and (c) powerful activation of AlcR by the physiological inducer, acetaldehyde, produced from growth substrates such as ethanol and l-threonine. We have previously characterized the chemical features of direct inducers of the alc regulon. These studies allowed us to predict which type of carbonyl compounds might induce the system. In this study we have determined that catabolism of different amino acids, such as L-valine, L-isoleucine, L-arginine and L-proline, produces aldehydes that are either not accumulated or fail to induce the alc system. On the other hand, catabolism of D-galacturonic acid and putrescine, during which aldehydes are transiently accumulated, gives rise to induction of the alc genes. We show that the formation of a direct inducer from carboxylic esters does not depend on alcA-encoded alcohol dehydrogenase I or on AlcR, and suggest that a cytochrome P450 might be responsible for the initial formation of a physiological aldehyde inducer.
Assuntos
Aspergillus nidulans/metabolismo , Etanol/metabolismo , Acetaldeído/metabolismo , Acetaldeído/farmacologia , Álcool Desidrogenase/genética , Álcool Desidrogenase/metabolismo , Aldeído Desidrogenase/genética , Aldeído Desidrogenase/metabolismo , Aminoácidos/metabolismo , Aminoácidos/farmacologia , Aspergillus nidulans/enzimologia , Aspergillus nidulans/genética , Hidrolases de Éster Carboxílico/metabolismo , Sistema Enzimático do Citocromo P-450/metabolismo , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Ésteres/química , Ésteres/metabolismo , Ésteres/farmacologia , Etanol/farmacologia , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Regulação Fúngica da Expressão Gênica/efeitos dos fármacos , Genes Fúngicos/efeitos dos fármacos , Genes Fúngicos/fisiologia , Genes Reguladores/fisiologia , Genótipo , Glicerol/farmacologia , Ácidos Hexurônicos/química , Ácidos Hexurônicos/metabolismo , Ácidos Hexurônicos/farmacologia , Lactonas/farmacologia , Lactose/metabolismo , Putrescina/metabolismo , Putrescina/farmacologia , Ácido gama-Aminobutírico/metabolismoRESUMO
The ethanol utilization (alc) pathway in Aspergillus nidulans is one of the strongest expressed gene systems in filamentous fungi. The pathway-specific activator AlcR requires the presence of an inducing compound to activate transcription of genes under its control. We have demonstrated recently that acetaldehyde is the sole physiological inducer of ethanol catabolism. In the present study we show that compounds with catabolism related to that of ethanol, i.e. primary alcohols, primary monoamines and l-threonine, act as inducers because their breakdown results in the production of inducing aliphatic aldehydes. Such aldehydes were shown to induce the alc genes efficiently at low external concentrations. When ethanol is mixed with representatives of another class of strong direct inducers, ketones, the physiological inducer, acetaldehyde, prevails as effector. Although direct inducers essentially carry a carbonyl function, not all aldehydes and ketones act as inducers. Structural features discriminating non-inducing from inducing compounds concern: (i) the length of the aliphatic side group(s); (ii) the presence and nature of any non-aliphatic substituent. These characteristics enable us to predict whether or not a given carbonyl compound will induce the alc genes.
