Substituent Effect of Phenolic Aldehyde Inhibition on Alcoholic Fermentation by Saccharomyces cerevisiae

Phenolic compounds significantly inhibit microbial fermentation of biomass hydrolysates. To understand the quantitative structure−inhibition relationship of phenolic aldehydes on alcoholic fermentation, the effect of 11 different substituted benzaldehydes on the final ethanol yield was examined. The results showed that the degree of phenolic benzaldehyde inhibition was strongly associated with the position of phenolic hydroxyl groups but not the number of phenolic hydroxyl groups. It was observed that ortho-substituted 2-hydroxybenzaldehyde resulted in 15−20-fold higher inhibition than the metaor parasubstituted analogues of 3and 4-hydroxybenzaldehydes. From the correlation of the molecular descriptors to inhibition potency in yeast fermentation, we found a strong relationship between the octanol/water partition coefficient (log P) of aldehydes and the EC50 value. The most inhibitory 2-hydroxybenzaldehyde has the highest log P and possesses an ortho −OH group capable of forming an intramolecular hydrogen bond, which can potentially increase the cell membrane permeability and toxicity. The results also indicated that the calculated free energy change between phenolic aldehydes and amino acids can be used to predict their structure−inhibitory activity relationship.