Abstract

S-adenosylmethionine (AdoMet) is a central metabolite required for methylation and sulfur metabolism, synthesized in Saccharomyces cerevisiae by the cytosolic enzymes Sam1 and Sam2. While transcriptional and metabolic regulation of AdoMet biosynthesis have been extensively studied, how metabolic state influences the spatial organization of AdoMet synthases remains incompletely understood. Herein, we show that Sam1 undergoes robust and reversible relocalization into cytosolic assemblies under low-glucose metabolic states. These assemblies are dynamic and dissolve rapidly upon glucose refeeding in a manner that requires metabolizable glucose, indicating regulation by metabolic flux. While Sam1 assemblies associate with stress granules during prolonged starvation, a substantial fraction form independently under acute low-glucose conditions, indicating that Sam1 relocalization is not fully coordinated with canonical stress granule formation. Untargeted metabolomic analysis indicates that AdoMet pools are broadly maintained, while a targeted fluorescence-based enzymatic assay detects a modest but reproducible reduction in AdoMet under low-glucose conditions. Together, these findings define a metabolically gated mechanism for reversible Sam1 sequestration and support a model in which spatial organization of metabolic enzymes is coupled to cellular metabolic state.

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