Faculty Opinions recommendation of Biosynthesis of medicinal tropane alkaloids in yeast.
Bibliographic record
Abstract
Tropane alkaloids (TAs) from nightshade plants are neurotransmitter inhibitors used for treating neuromuscular disorders and are classified as essential medicines by the World Health Organization 1,2 .Global supply challenges have resulted in frequent drug shortages 3,4 .Further supply-chain vulnerabilities are revealed by events like the Australian wildfires 5 and the COVID-19 pandemic 6 .Rapidly deployable production strategies that are robust to environmental and socioeconomic upheaval 7,8 are needed.Here, we engineered baker's yeast to produce the medicinal TAs hyoscyamine and scopolamine starting from simple sugars and amino acids.We combined functional genomics to identify a missing pathway enzyme, protein engineering to enable functional acyltransferase expression via trafficking to the vacuole, heterologous transporters to facilitate intracellular routing, and strain optimization to improve titers.Our integrated system positions >20 proteins adapted from yeast, bacteria, plants, and animals across six sub-cellular locations to recapitulate the spatial organization of TA biosynthesis in plants.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.006 |
| Meta-epidemiology (narrow) | 0.003 | 0.001 |
| Meta-epidemiology (broad) | 0.002 | 0.002 |
| Bibliometrics | 0.005 | 0.007 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.003 | 0.002 |
| Open science | 0.003 | 0.002 |
| Research integrity | 0.002 | 0.002 |
| Insufficient payload (model declined to judge) | 0.085 | 0.102 |
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 source (direct Gemma or distilled Codex), 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".