Sal is a proteobacterial bile acid aldolase that repurposes key thiolase catalytic residues for retroaldol cleavage of C5 steroid side chains
Bibliographic record
Abstract
Aldolases hold potential as biocatalysts for synthesis of novel steroid pharmaceuticals. The steroid aldolase from Comamonas testosteroni ( Ct Sal) forms a complex with C. testosteroni steroid hydratase ( Ct Shy). Ct Sal cleaves the C 5 side chain of bile acid thioester steroids, whereas a previously characterized actinobacterial homolog from Thermonospora curvata ( Tc Ltp2) targets the C 3 side chain. We identified Tyr302 and Cys304 as the catalytic residues in Ct Sal, different from the paired Tyr residues found in Tc Ltp2. The 1.95 Å structure of Ct Sal bound to the C-terminal domain of unknown function 35 (DUF35) of Ct Shy ( Ct Shy DUF35 – Ct Sal) reveals a central Ct Sal dimer flanked by two Ct Shy DUF35 domains in an αββα arrangement. Ct Shy DUF35 has a unique Cys 3 His 1 (C 3 H 1 ) zinc finger that shapes the substrate-binding cleft of Ct Sal, preventing the binding of the flat cholesterol rings while accommodating the bent rings of bile acids. Phylogenetically, Sals and Ltp2s form separate clades and are distantly related to thiolases. Intriguingly, a Trypanosoma brucei homolog, annotated as a thiolase-like protein ( Tb SLP), shares catalytic architecture of Ct Sal, suggesting an aldolase rather than a thiolase function. This study provides the first detailed characterization of a C 5 side chain steroid aldolase, revealing its unique catalytic features and expanding our understanding of steroid side chain catabolism in Proteobacteria.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".