Selective inhibition of growth by the proline analogue thiazolidine-4-carboxylic acid and its probable mode of action in Saccharomyces cerevisiae.

Cells of Saccharomyces cerevisiae showed differential growth inhibition when cultured on various carbon sources in the presence of the proline analogue thiazolidine-4-carboxylic acid (TZ). On 0.5% yeast extract, 2% glucose and TZ (10 mg/ml) medium, growth lags from 8 to 10 h were observed, after which cells recovered and growth proceeded normally. Growth was totally inhibited on a medium of 0.5% yeast extract, 3% ethanol, and 5 mg of TZ per ml. This inhibition was not due to the inability of cells to undergo aerobic respiration, since similar media containing glycerol instead of ethanol allowed growth. Proline added to the culture medium reversed the lag on glucose and TZ medium but did not promote recovery on ethanol and TZ medium. TZ was found to have two probable modes of action in yeast. It was a noncompetitive inhibitor of yeast alcohol dehydrogenase, and it was also found to be incorporated into cellular protein. Uptake studies using (14)C-labeled TZ showed that the recovery on glucose was correlated with the progressive exclusion of the analogue from cells.