MET2
S. cerevisiae
homoserine O-acetyltransferase
What the model saw
Gene: MET2 Organism: Saccharomyces cerevisiae Known functions: homoserine O-acetyltransferase. acyltransferase activity, transferring groups other than amino-acyl groups. homoserine O-acetyltransferase activity.
View unredacted entry
homoserine O-acetyltransferase. acyltransferase activity, transferring groups other than amino-acyl groups. homoserine O-acetyltransferase activity.
Solver output
MET2 encodes homoserine O-acetyltransferase, which catalyzes the first committed step in the methionine biosynthesis pathway in S. cerevisiae, converting homoserine to O-acetylhomoserine. Methionine availability is a critical regulator of aging: methionine restriction is well-established to extend lifespan in multiple organisms, and intracellular methionine levels modulate S-adenosylmethionine (SAM) pools, which feed into one-carbon metabolism and methylation reactions. By producing methionine, MET2 activity increases methionine and SAM availability, which can activate the TORC1 nutrient-sensing pathway (methionine is a key amino acid sensed by TORC1/mTOR). However, the normal function of MET2 is to sustain methionine biosynthesis, which is essential for growth and proteostasis; loss of MET2 mimics methionine restriction and has been shown to extend chronological and replicative lifespan in yeast. Therefore, the normal (active) function of MET2 promotes methionine sufficiency and TORC1 activation, opposing the longevity benefits of methionine restriction, making it anti-longevity in its normal role.
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 correctly identified the mechanistic role of MET2 in methionine biosynthesis and correctly reasoned that MET2 promotes methionine sufficiency/TORC1 activation, which opposes longevity benefits of methionine restriction — making it anti-longevity. However, the model's final prediction was "pro_longevity" despite its own reasoning concluding the opposite. This is a contradiction within the model's output: the reasoning correctly points to anti_longevity but the final label says pro_longevity. The mechanism described is largely correct, but the final answer is wrong. This appears to be a failure where the model's reasoning and conclusion are misaligned.
Raw API responses
solver
{
"reasoning": "MET2 encodes homoserine O-acetyltransferase, which catalyzes the first committed step in the methionine biosynthesis pathway in S. cerevisiae, converting homoserine to O-acetylhomoserine. Methionine availability is a critical regulator of aging: methionine restriction is well-established to extend lifespan in multiple organisms, and intracellular methionine levels modulate S-adenosylmethionine (SAM) pools, which feed into one-carbon metabolism and methylation reactions. By producing methionine, MET2 activity increases methionine and SAM availability, which can activate the TORC1 nutrient-sensing pathway (methionine is a key amino acid sensed by TORC1/mTOR). However, the normal function of MET2 is to sustain methionine biosynthesis, which is essential for growth and proteostasis; loss of MET2 mimics methionine restriction and has been shown to extend chronological and replicative lifespan in yeast. Therefore, the normal (active) function of MET2 promotes methionine sufficiency and TORC1 activation, opposing the longevity benefits of methionine restriction, making it anti-longevity in its normal role.",
"confidence": 0.72,
"key_pathways": [
"methionine biosynthesis",
"S-adenosylmethionine (SAM) / one-carbon metabolism",
"TORC1 nutrient sensing"
],
"mechanism_class": "deregulated_nutrient_sensing",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model correctly identified the mechanistic role of MET2 in methionine biosynthesis and correctly reasoned that MET2 promotes methionine sufficiency/TORC1 activation, which opposes longevity benefits of methionine restriction — making it anti-longevity. However, the model's final prediction was \"pro_longevity\" despite its own reasoning concluding the opposite. This is a contradiction within the model's output: the reasoning correctly points to anti_longevity but the final label says pro_longevity. The mechanism described is largely correct, but the final answer is wrong. This appears to be a failure where the model's reasoning and conclusion are misaligned.",
"failure_mode": "right_answer_wrong_reasoning",
"answer_correct": false,
"mechanism_correct": true,
"reasoning_quality": 3,
"ground_truth_questionable": false
}