Melatonin and other 5-methoxylated indoles in yeast: Presence in high concentrations and dependence on tryptophan availability

Abstract

Melatonin (MLT) and two structurally related compounds, 5-methoxytryptamine (5MT) and 5-methoxytryptophol (5 ML), are formed in Saccharomyces cerevisiae in high concentrations. Depending on conditions, levels can attain several ng/mg protein, sometimes more than 10 (MLT, 5MT) or 20 (up to >100: 5 ML) ng/mg. Starvation in salt medium leads to a drop in all methoxyindoles below detection thresholds. After 4 h in salt, reincubation in growth medium restores high levels. Addition of tryptophan, serotonin or N-acetylserotonin to starved cells also elevates MLT and 5MT Exogenous MLT (50 or 100 μM) causes 5MT to rise above 700 ng/mg protein within 0.5 h, whereas same concentrations of exogenous 5MT lead to >90->300 ng MLT/mg. Therefore, MLT can be synthesized via the most common pathway from tryptophan to N-acetylserotonin as a direct precursor, and is deacetylated to 5MT; biosynthesis of MLT by N-acetylation of 5MT is a secondary pathway.