Bioproduction platform using a novel cane toad (Rhinella marina) N-methyltransferase for psychedelic-inspired drug discovery
Bibliographic record
Abstract
Abstract Psychedelic indolethylamines have emerged as potential medicines to treat several psychiatric pathologies. Natural sources of these compounds include 'magic mushrooms', plants used to prepare ahayuasca, and toads. Owing to the occurrence of indolethylamines such as N,N -dimethyltryptamine, toad skin and parotid gland preparations have a history of ceremonial use, yet their biosynthesis remains uncharacterized. We report the isolation of an indolethylamine N -methyltransferase (RmNMT) from cane toad ( Rhinella marina ). Unlike functionally similar mammalian and fungal enzymes, the efficiency and promiscuity of RmNMT made it suitable for the bioproduction of new-to-nature indolethylamine derivatives. N,N -Dimethylated indolethylamines showed reduced affinity and engagement at 5-HT 1A and 5-HT 2A receptors respectively, compared with primary amine equivalents. Despite reduced 5-HT 2A receptor engagement of tertiary amines, only these molecules induced hallucinogenic behavior in mice underscoring the importance of metabolic stability. The discovery of RmNMT facilitated the establishment of a bioproduction platform for the isolation and pharmacological screening of novel indolethylamines.
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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 | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.001 |
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".