Suppressive Effects of Natural Compounds on Methionine Auxotrophy of a Cu,Zn-Superoxide Dismutase-Deficient Mutant of Saccharomyces cerevisiae

Yeast lacking Cu,Zn-superoxide dismutase (sod1 Delta) exhibits methionine (Met) auxotrophy, primarily due to the depletion of NADPH required in the sulfur assimilation pathway by oxidative stress. In this study, we measured the ability of natural compounds, including ingredients in foods and dietary supplements, to restore the cell growth of sod1 Delta in liquid and solid media without Met. Homocysteine at around 0.1 mM fully suppressed auxotrophy but in excess (> 0.4 mM) had a harmful effect. Methionine sulfoxide at concentrations from 0.05 to 0.8 mM and S-adenosylmethione (0.05 to 6.2 mM) completely relieved the growth defects caused by sod1 Delta. Ascorbic acid (1 to 50 mM) restored sod1 Delta growth, indicating that the action of this antioxidant could improve Met biosynthesis. However, ascorbic acid derivatives, ascorbic acid 2-glucoside and dehydroascorbic acid, did not show any activity. The suppressive effects of cysteine, N-acetylcysteine, and glutathione peaked at 0.1 mM, 0.5 mM, and 0.05 mM, respectively, but an excess of these agents was less effective. Suppression by dithiothreitol confirms that the thiol group is responsible for the amelioration of Met biosynthesis. No growth was restored for other categories of antioxidants including polyphenols, Trolox, melatonin, astaxanthin, and others.