Evidence for chaotropicity/kosmotropicity offset in a yeast growth model

Chaotropes are compounds which cause the disordering, unfolding and denaturation of biological macromolecules. It is the chaotropicity of fermentation products that often acts as the primary limiting factor in ethanol and butanol fermentations. Since ethanol is mildly chaotropic at low concentrations, it prevents the growth of the producing microbes via its impacts on a variety of macromolecular systems and their functions. Kosmotropes have the opposite effect to chaotropes and we hypothesised that it might be possible to use these to mitigate chaotrope-induced inhibition of Saccharomyces cerevisiae growth. We also postulated that kosmotrope-mediated mitigation of chaotropicity is not quantitatively predictable. The chaotropes ethanol and urea, and compatible solutes glycerol and betaine (kosmotrope), and the highly kosmotropic salt ammonium sulphate all inhibited the growth rate of Saccharomyces cerevisiae in the concentration range 5-15%. They resulted in increased lag times, decreased maximum specific growth rates, and decreased final optical densities. Surprisingly, neither the stress protectants nor ammonium sulphate reduced the inhibition of growth caused by ethanol. Whereas, in some cases, compatible solutes and kosmotropes mitigated against the inhibitory effects of urea. However, this effect was not mathematically additive from the quantification of chao-/kosmotropicity of each individual compound. The potential effects of glycerol, betaine and/or ammonium sulphate may have been reduced or masked by the metabolic production of compatible solutes. It may nevertheless be that the addition of kosmotropes to fermentations which produce chaotropic products can enhance metabolic activity, growth rate, and/or product formation.