Metabolism of the Melatonin Metabolite N¹-Acetyl-N²-formyl-5-methoxykynuramine in Saccharomyces cerevisiae

Abstract

In yeast, melatonin had previously been shown to be formed and to be metabolized to other 5-methoxylated indoles. We now demonstrate that an alternate melatonin metabolite, N¹-acetyl-N²-formyl-5-methoxykynuramine (AFMK), is converted by S. cerevisiae to N¹-acetyl-5-methoxykynuramine (AMK), which is subsequently released to the culture medium. By means of an NO donor, PAPA-NONOate, AMK extracted from the medium is nitrosated to 3-acetamidomethyl-6-methoxycinnolinone (AMMC). The deformylation of AFMK was enhanced by aspartate or glutamine. This is not a general phenomenon of providing nitrogen sources, since asparagine and arginine were slightly, and guanidine strongly inhibitory, whereas addition of ammonium caused only small increases. Experiments with glutamine or high ammonium indicate the formation of another metabolite, N-[2-(6-methoxyquinazolin-4-yl)-ethyl]-acetamide (MQA).