Elucidation of toxicity of organic acids inhibiting growth of Escherichia coli W

The toxic effects of 3-hydroxypropionic acid (3-HP) at high concentrations on cell growth and cellular metabolism are a great challenge to its commercial production. This study has examined and compared the toxic effects of 3-HP on cell growth with other similar weak acids, especially lactic acid, under various concentrations, temperatures and pH using Escherichia coli W as the test strain. 3-HP was approximately 4.4-times more toxic than lactic acid due to the 4.4-fold weaker acidity or 0.64 higher pKa value. The two acids presented no appreciable difference when the growth inhibition was correlated with the undissociated or protonated free acid concentration calculated by the Henderson-Hasselbalch equation. The growth inhibition by other small organic acids, such as acetic acid, pyruvic acid, propionic acid, 2-hydroxybutyric acid (2-HB) and 3-hydroxybutyric acid (3-HB), was also well correlated with their pKa values or protonated free acid concentrations. This study suggests that the growth inhibition by small weak acids is mainly caused by the socalled proton effect (rather than the anion effect), i.e., an increase in the intracellular proton concentration. An appropriate increase in the medium pH was suggested to alleviate the acid toxicity by reducing the free acid concentration in the culture medium.