Overexpression of ADH1 confers hyper-resistance to formaldehyde in Saccharomyces cerevisiae.
In an attempt to clone genes involved in resistance to formaldehyde we have screened a genomic library based on the episomal plasmid YEp24 for the ability to increase resistance to formaldehyde in a wild-type strain. In addition to SFA, the gene encoding the formaldehyde dehydrogenase Adh5, an enzyme most potent in formaldehyde de-toxification, we isolated a second plasmid that conferred a less pronounced but significant hyper-resistance to formaldehyde. Its passenger DNA contained the gene ADH1, encoding alcohol dehydrogenase 1 (EC 1.1.1.1), which could be shown to be responsible for the observed hyper-resistance phenotype. Construction of an adh1-0 mutant revealed that yeast lacking a functional ADH1 gene is sensitive to formaldehyde. While glutathione is essential for Adh5-mediated formaldehyde de-toxification, Adh1 reduced formaldehyde best in the absence of this thiol compound. Evidence is presented that formaldehyde is a substrate for Adh1 in vivo and in vitro and that its cellular de-toxification employs a reductive step that may yield methanol.
Grey
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Institut für Mikrobiologie, J. W. Goethe-Universitat, Theodor-Stern-Kai 7, Haus 75, D-60590 Frankfurt am Main, Germany.
Schmidt
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M
Brendel
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D000433:1-Propanol / Q000494:pharmacology; D000426:Alcohol Dehydrogenase / Q000235:genetics / Q000378:metabolism*; D003001:Cloning, Molecular; D004352:Drug Resistance, Microbial; D005557:Formaldehyde / Q000378:metabolism* / Q000494:pharmacology*; D005800:Genes, Fungal; D010641:Phenotype; D020005:Propanols; D012441:Saccharomyces cerevisiae / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D013379:Substrate Specificity
D020005:Propanols; D005557:Formaldehyde; C006463:allyl alcohol; D000433:1-Propanol; D000426:Alcohol Dehydrogenase