Regulatory Networks Governing Methionine Catabolism into Volatile Organic Sulfur-Containing Compounds in Clonostachys .

Adaptation to environmental perturbations requires living systems to coordinately regulate signaling pathways, gene expression, and metabolism. To better understand the mechanisms underlying adaptation, the regulatory nodes within networks must be elucidated. Here, (which encodes an aminotransferase), (which encodes a decarboxylase), and (which encodes a demethiolase) were identified as key genes involved in the catabolism of methionine in the mycoparasitic fungus , isolated from ascocarps. Exogenous Met induced the transcription of and but repressed the transcription of , which is controlled by the putative MSN2 and GLN3 binding sites responding to nitrogen catabolite repression. Met and its structural derivatives function as glutamine synthetase inhibitors, resulting in the downregulation of expression. The putative GLN3 binding site was necessary for downregulation. In , Met and its structural derivatives also triggered downregulation of demethiolase gene expression. Altogether, the results indicated that exogenous Met triggered nitrogen catabolite repression, which stimulated the Ehrlich pathway and negatively regulated the demethiolation pathway via the methionine sulfoximine-responsive regulatory pathway. This finding revealed the regulatory nodes within the networks controlling the catabolism of Met into volatile organic sulfur-containing compounds, thereby enhancing our understanding of adaptation. Methionine shuttles organic nitrogen and plays a central role in nitrogen metabolism. Exogenous Met strongly induces the expression of and , represses the expression of , and generates volatile organic sulfur-containing compounds via the Ehrlich and demethiolation pathways. In this study, we used genetic, bioinformatic, and metabolite-based analyses to confirm that transcriptional control of the aminotransferase gene , the decarboxylase gene , and the demethiolase gene modulates Met catabolism into volatile organic sulfur-containing compounds. Importantly, we found that, in addition to the Ehrlich pathway, the demethiolation pathway was regulated by a nitrogen catabolite repression-sensitive regulatory pathway that controlled the transcription of genes required to catabolize poor nitrogen sources. This work significantly advances our understanding of nitrogen catabolite repression-sensitive transcriptional regulation of sulfur-containing amino acid catabolism and provides a basis for engineering Met catabolism pathways for the production of fuel and valuable flavor alcohols.