Elucidation of Gephyronic Acid Biosynthetic Pathway Revealed Unexpected SAM-Dependent Methylations
Bibliographic record
Abstract
Gephyronic acid, a cytostatic polyketide produced by the myxobacterium Cystobacter violaceus Cb vi76, exhibits potent and selective eukaryotic protein synthesis inhibition. Next-generation sequencing of the C. violaceus genome revealed five type I polyketide synthases and post-PKS tailoring enzymes including an O-methyltransferase and a cytochrome P450 monooxygenase. Seven methyltransferase (MT) domains embedded within the PKS subunits were found to install the methyl branches throughout the gephyronic acid skeleton. A rare loading domain from the GNAT superfamily also contains an embedded MT domain that catalyzes the in situ production of an isobutyryl starter unit. Phylogenetic analysis identified new motifs that distinguish MT domains located in PKS pathways with in cis acyltransferase (AT) domains from MT domains located in PKS pathways with trans AT enzymes. The identification of the gene cluster sets the stage for the generation of a heterologous expression system, which will allow further investigation of selective eukaryotic protein synthesis inhibitors through the generation of gephyronic acid analogues.
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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 | 0.003 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 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 | 0.001 |
| 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".