BNA2
S. cerevisiae
dioxygenase BNA2
What the model saw
Gene: BNA2 Organism: Saccharomyces cerevisiae Known functions: dioxygenase BNA2. L-tryptophan 2,3-dioxygenase activity. heme binding. indoleamine 2,3-dioxygenase activity. metal ion binding. oxidoreductase activity, acting on single donors with incorporation of molecular oxygen, incorporation of two atoms of oxygen.
View unredacted entry
dioxygenase BNA2. L-tryptophan 2,3-dioxygenase activity. heme binding. indoleamine 2,3-dioxygenase activity. metal ion binding. oxidoreductase activity, acting on single donors with incorporation of molecular oxygen, incorporation of two atoms of oxygen.
Solver output
BNA2 encodes the tryptophan 2,3-dioxygenase (TDO) in S. cerevisiae, catalyzing the first and rate-limiting step of the kynurenine pathway, which converts L-tryptophan to N-formylkynurenine. This pathway is the primary route for de novo NAD+ biosynthesis (the "BNA" pathway — Biosynthesis of Nicotinic Acid). NAD+ is a critical cofactor for sirtuins (Sir2 in yeast), which are NAD+-dependent deacetylases that extend replicative and chronological lifespan by regulating gene silencing, DNA repair, and metabolic homeostasis. Maintaining flux through the kynurenine/BNA pathway sustains intracellular NAD+ levels, thereby supporting sirtuin activity and nutrient-sensing regulation. Loss of BNA2 would deplete NAD+ pools and impair Sir2-dependent longevity mechanisms, making its normal function pro-longevity.
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 but the ground truth is anti_longevity. The model's reasoning about BNA2's role in the kynurenine/NAD+ biosynthesis pathway is partially correct in terms of biochemistry, but the conclusion is wrong. BNA2 is actually anti-longevity in yeast - deletion of BNA2 extends lifespan rather than shortening it. The model assumed that because NAD+ supports Sir2 activity, BNA2 must be pro-longevity, but this overlooks the fact that the kynurenine pathway also produces toxic metabolites and that tryptophan catabolism through this pathway can be detrimental to longevity. The model was fairly confident (0.72) in its wrong answer. The mechanistic reasoning about NAD+ and sirtuins sounds plausible but leads to the wrong conclusion about the direction of effect on longevity.
Raw API responses
solver
{
"reasoning": "BNA2 encodes the tryptophan 2,3-dioxygenase (TDO) in S. cerevisiae, catalyzing the first and rate-limiting step of the kynurenine pathway, which converts L-tryptophan to N-formylkynurenine. This pathway is the primary route for de novo NAD+ biosynthesis (the \"BNA\" pathway — Biosynthesis of Nicotinic Acid). NAD+ is a critical cofactor for sirtuins (Sir2 in yeast), which are NAD+-dependent deacetylases that extend replicative and chronological lifespan by regulating gene silencing, DNA repair, and metabolic homeostasis. Maintaining flux through the kynurenine/BNA pathway sustains intracellular NAD+ levels, thereby supporting sirtuin activity and nutrient-sensing regulation. Loss of BNA2 would deplete NAD+ pools and impair Sir2-dependent longevity mechanisms, making its normal function pro-longevity.",
"confidence": 0.72,
"key_pathways": [
"kynurenine/NAD+ biosynthesis pathway",
"sirtuin (Sir2) NAD+-dependent deacetylase signaling",
"tryptophan catabolism"
],
"mechanism_class": "deregulated_nutrient_sensing",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model predicted pro_longevity but the ground truth is anti_longevity. The model's reasoning about BNA2's role in the kynurenine/NAD+ biosynthesis pathway is partially correct in terms of biochemistry, but the conclusion is wrong. BNA2 is actually anti-longevity in yeast - deletion of BNA2 extends lifespan rather than shortening it. The model assumed that because NAD+ supports Sir2 activity, BNA2 must be pro-longevity, but this overlooks the fact that the kynurenine pathway also produces toxic metabolites and that tryptophan catabolism through this pathway can be detrimental to longevity. The model was fairly confident (0.72) in its wrong answer. The mechanistic reasoning about NAD+ and sirtuins sounds plausible but leads to the wrong conclusion about the direction of effect on longevity.",
"failure_mode": "confident_wrong",
"answer_correct": false,
"mechanism_correct": false,
"reasoning_quality": 2,
"ground_truth_questionable": false
}