MET7 (YOR241W, Q08645) review notes

Context: YeastPathways module aspartate_family_threonine_biosynthesis; YeastCyc assigns MET7 to the
folate polyglutamylation reaction (EC 6.3.2.17) in several pathways/superpathways.

Evidence journal

• Identity/activity: FPGS is encoded by MET7 PMID:10799479; first glutamate added by FOL3 (dihydrofolate synthetase) PMID:10799479.
• Compartments: FPGS activity in cytoplasm and mitochondria PMID:10775416. MET7 "appears to encode both the cytoplasmic and mitochondrial forms" PMID:10775416.
• Conflict: Cherest et al. argue the mitochondrial phenotype is not due to missing mitochondrial FPGS PMID:10799479; DeSouza et al. attribute petite formation to dTMP deficiency PMID:10775416.
• Methionine: met7 is a methionine auxotroph PMID:10775416; cytoplasmic FPGS alone rescues PMID:10775416. Mechanism: Met6 needs polyglutamyl 5-CH3-THF, so the MET7 link to methionine biosynthesis is co-substrate supply (kept non-core).
• ER (HDA, N-terminal SWAT-GFP) is likely a tag artefact PMID:26928762.
• Inner membrane / matrix: UniProt by similarity only [UniProt:Q08645].

Pathway observations

• P4-PWY-1 (threonine+methionine superpathway) gives MET7 "L-threonine metabolic process" by RCA: removed (pure superpathway inflation).
• PWY3O-20 maps to "folic acid metabolic process": modified to tetrahydrofolylpolyglutamate biosynthetic process.
• MET7 does not belong in a threonine module; it is a one-carbon/methionine-branch cofactor enzyme.