An Engineered Allele of <i>afsQ1</i> Facilitates the Discovery and Investigation of Cryptic Natural Products
Bibliographic record
Abstract
New approaches to antimicrobial discovery are needed to address the growing threat of antibiotic resistance. The Streptomyces genus, a proven source of antibiotics, is recognized as having a large reservoir of untapped secondary metabolic genes, many of which are likely to produce uncharacterized compounds. However, most of these compounds are currently inaccessible, as they are not expressed under standard laboratory conditions. Here, we present a novel methodology for activating these "cryptic" metabolites by heterologously expressing a constitutively active pleiotropic regulator. By screening wild Streptomyces isolates, we identified the antibiotic siamycin-I, a lasso peptide that we show is active against multidrug pathogens. We further revealed that siamycin-I interferes with cell wall integrity via lipid II. This new technology has the potential to be broadly applied for use in the discovery of additional "cryptic" metabolites.
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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 | 0.001 |
| 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".