Enzyme Optimization and Process Development for a Scalable Synthesis of (<i>R</i>)-2-Methoxymandelic Acid
Why this work is in the frame
A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.
Bibliographic record
Abstract
The rational protein engineering of wild type BCJ2315 nitrilase and its use in the development of a one-pot, enantioselective, dynamic kinetic resolution for (R)-2-methoxymandelic acid is reported. Through a combination of molecular docking and B-factor analyses, a focused library of mutants was identified and screened to improve nitrilase selectivity, activity, and stability. Initial optimization revealed that the addition of sodium bisulfite prevented enzyme deactivation by the aldehyde starting material, removing the need to isolate the cyanohydrin and allowing for development of a one-pot process for mutant screening. Further optimization of the process with the preferred mutants revealed subtle interactions between temperature, pH, substrate loading, and enzyme source which ultimately led to development of a suitable lyophilized whole cell process for scale-up, affording (R)-2-methoxymandelic acid in 97% ee and 70% isolated yield on multigram scale.
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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 | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 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 it