A Novel Aldehyde Reductase Encoded by YML131W from Saccharomyces cerevisiae Confers Tolerance to Furfural Derived from Lignocellulosic Biomass Conversion

Abstract

Furfural is one of the main aldehyde inhibitors generated during the pretreatment of lignocellulosic biomass. Saccharomyces cerevisiae can in situ detoxify furfural to the less toxic furan methanol (FM) via the activities of multiple dehydrogenases/reductases. In this study, we report that an uncharacterized gene, YML131W, was highly induced under furfural stress conditions and that the transcription factors Yap1p, Msn2/4p, and/or Hsf1p likely controlled its upregulated expression. The induced transcription of YML131W led to higher concentrations of its encoded protein. Enzyme activity assays showed that YML131W is an aldehyde reductase that plays a role in detoxifying furfural to FM. YML131W also showed activity toward other aldehydes, suggesting that it is involved in detoxifying endogenous toxic aldehydes generated via the degradation of misfolded and damaged proteins. This detoxification role would help to maintain cell viability under furfural stress conditions. A S. cerevisiae strain overexpressing YML131W showed increased tolerance to furfural. YML131W was able to catalyze the conversion of formaldehye, acetaldehyde, propionaldehyde, and butyaldehyde to their corresponding alcohols, indicating that it has potential applications in producing fuels such as butanol and isobutanol. A phylogenetic analysis grouped YML131W into the leukotriene B4 dehydrogenases (LTD) family, but its amino acid sequence substantially differed from those of other proteins in the LTD family. We identified 15 proteins from 14 yeast species that showed sequence similarities to YML131W. These other proteins likely have similar functions to that of YML131W and may have potential to confer tolerance to aldehyde inhibitors derived from the lignocellulosic biomass conversion process.