Reconstruction of Cladoniamide Biosynthesis Reveals Nonenzymatic Routes to Bisindole Diversity
Bibliographic record
Abstract
Indolotryptolines are bisindole natural products isolated from microbial and eDNA sources. Here, we report the sequence of transformations that convert an indolocarbazole to the indolotryptoline cladoniamide through reconstruction of the four-enzyme cascade in E. coli. This cascade involves, first, conversion of an indolocarbozole to a C4c-C7a cis diol by ClaX1; second, N-methylation by ClaM1; third, rearrangement to the indolotryptoline scaffold by ClaX2; and fourth, installation of an O-methyl group by ClaM3. We furthermore elucidate the origins of minor cladoniamides D-G as the products of nonenzymatic, base-catalyzed opening of the succinimide ring of cladonimiades A-B. Overall, this work reveals the precarious pathway indolocarbazole-derived metabolites must traverse as they are converted into indolotryptoline products and highlights the importance of nonenzymatic chemistry in generating bisindole diversity.
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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) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| 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 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".