MET17
S. cerevisiae
bifunctional cysteine synthase/O-acetylhomoserine aminocarboxypropyltransferase MET17
What the model saw
Gene: MET17 Organism: Saccharomyces cerevisiae Known functions: bifunctional cysteine synthase/O-acetylhomoserine aminocarboxypropyltransferase MET17. O-acetylhomoserine aminocarboxypropyltransferase activity. O-acetylhomoserine sulfhydrylase activity. cysteine synthase activity. pyridoxal phosphate binding. transferase activity, transferring alkyl or aryl (other than methyl) groups.
View unredacted entry
bifunctional cysteine synthase/O-acetylhomoserine aminocarboxypropyltransferase MET17. O-acetylhomoserine aminocarboxypropyltransferase activity. O-acetylhomoserine sulfhydrylase activity. cysteine synthase activity. pyridoxal phosphate binding. transferase activity, transferring alkyl or aryl (other than methyl) groups.
Solver output
MET17 encodes a bifunctional enzyme central to sulfur amino acid metabolism in yeast, catalyzing the final steps in both cysteine and methionine biosynthesis via O-acetylhomoserine sulfhydrylase and cysteine synthase activities. Cysteine is the rate-limiting precursor for glutathione (GSH) biosynthesis, the primary intracellular antioxidant; adequate cysteine supply supports robust GSH levels, reducing oxidative damage that drives aging. Methionine, the other product pathway, feeds into the methionine cycle and S-adenosylmethionine (SAM) production, which is critical for methylation reactions including epigenetic regulation. Loss of MET17 in yeast leads to cysteine and methionine auxotrophy, impairing GSH-mediated redox homeostasis and proteostasis. Studies in yeast have shown that sulfur amino acid metabolism, particularly cysteine availability and GSH synthesis, is tightly linked to chronological and replicative lifespan, with methionine restriction being a known pro-longevity intervention—however, MET17's role in cysteine/GSH synthesis tips the balance toward pro-longevity by supporting antioxidant defense.
GenAge curators classify each gene's normal function as promoting (Pro-Longevity) or opposing (Anti-Longevity) longevity, based on synthesis across studies. Loss-of-function effects can vary from this depending on the manipulation.
Advisor judgment
The model predicted pro_longevity with 0.72 confidence, but the ground truth is anti_longevity. The model's reasoning is plausible on the surface — MET17 does participate in cysteine/methionine biosynthesis, and cysteine is a GSH precursor — but the conclusion is wrong. The model failed to account for the fact that MET17 (and sulfur amino acid metabolism more broadly) can have anti-longevity effects in yeast. Notably, methionine restriction extends lifespan in yeast, and MET17 activity supports methionine biosynthesis, which would be anti-longevity. The model actually acknowledged methionine restriction as pro-longevity but then rationalized away this key point by emphasizing the cysteine/GSH angle. The mechanistic reasoning is internally inconsistent and ultimately leads to the wrong conclusion. Confidence of 0.72 is inappropriately high for a wrong answer.
Raw API responses
solver
{
"reasoning": "MET17 encodes a bifunctional enzyme central to sulfur amino acid metabolism in yeast, catalyzing the final steps in both cysteine and methionine biosynthesis via O-acetylhomoserine sulfhydrylase and cysteine synthase activities. Cysteine is the rate-limiting precursor for glutathione (GSH) biosynthesis, the primary intracellular antioxidant; adequate cysteine supply supports robust GSH levels, reducing oxidative damage that drives aging. Methionine, the other product pathway, feeds into the methionine cycle and S-adenosylmethionine (SAM) production, which is critical for methylation reactions including epigenetic regulation. Loss of MET17 in yeast leads to cysteine and methionine auxotrophy, impairing GSH-mediated redox homeostasis and proteostasis. Studies in yeast have shown that sulfur amino acid metabolism, particularly cysteine availability and GSH synthesis, is tightly linked to chronological and replicative lifespan, with methionine restriction being a known pro-longevity intervention—however, MET17's role in cysteine/GSH synthesis tips the balance toward pro-longevity by supporting antioxidant defense.",
"confidence": 0.72,
"key_pathways": [
"glutathione biosynthesis via cysteine supply",
"sulfur amino acid metabolism (cysteine and methionine biosynthesis)",
"redox homeostasis and oxidative stress resistance"
],
"mechanism_class": "other",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model predicted pro_longevity with 0.72 confidence, but the ground truth is anti_longevity. The model's reasoning is plausible on the surface — MET17 does participate in cysteine/methionine biosynthesis, and cysteine is a GSH precursor — but the conclusion is wrong. The model failed to account for the fact that MET17 (and sulfur amino acid metabolism more broadly) can have anti-longevity effects in yeast. Notably, methionine restriction extends lifespan in yeast, and MET17 activity supports methionine biosynthesis, which would be anti-longevity. The model actually acknowledged methionine restriction as pro-longevity but then rationalized away this key point by emphasizing the cysteine/GSH angle. The mechanistic reasoning is internally inconsistent and ultimately leads to the wrong conclusion. Confidence of 0.72 is inappropriately high for a wrong answer.",
"failure_mode": "confident_wrong",
"answer_correct": false,
"mechanism_correct": false,
"reasoning_quality": 2,
"ground_truth_questionable": false
}