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 anh1-0 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.