Nitrogen source-dependent inhibition of yeast growth by glycine and its N-methylated derivatives

The effect of nitrogen source on the inhibitory properties of glycine and its N-methylated derivatives N-methylglycine (sarcosine), N,N-dimethylglycine, N,N,N-trimethylglycine (glycine betaine) on yeast growth was investigated. On solid minimal medium, all four glycine species completely or partially inhibited growth of Kluyveromyces lactis, Komagataella pastoris, Ogataea arabinofermentans, Spathaspora passalidarum and Yamadazyma tenuis at concentrations 5-10 mM when 10 mM NH₄Cl was the sole source of nitrogen. If NH₄Cl was substituted by sodium L-glutamate as the sole source of nitrogen, obvious growth inhibition by glycine and its N-methylated derivatives was generally not observed in any of these species. No obvious growth inhibition by any of the glycine species at a concentration of 10 mM was observed in Cyberlindnera jadinii, Lipomyces starkeyi, Lodderomyces elongisporus, Scheffersomyces stipitis or Yarrowia lipolytica on solid minimal medium irrespective of whether the nitrogen source was NH₄Cl or sodium L-glutamate. Growth inhibition assays of K. pastoris in liquid minimal medium supplemented with increasing concentrations of N,N-dimethylglycine demonstrated inhibitory effects for nine tested nitrogen sources. In most cases, N,N-dimethylglycine supplementation caused a decrease in growth efficiency that appeared to be proportional to the concentration of N,N-dimethylglycine. The biological relevance of these results is discussed.