Characterization of transglutaminase homologues found in andrimid biosynthesis
Bibliographic record
Abstract
Nonribosomal peptide synthetases (NRPSs) are multimodular enzymes that synthesize products with diverse structures and activities ranging from antibiotics to industrial solvents. They are arranged into an assembly line of modules where each module is responsible for incorporating a specific monomer into the final nonribosomal peptide (NRP). Diversity in NRPs stems from the fact that NRPSs utilize not only the 20 proteinogenic amino acids, but also include nonproteinogenic amino acids, fatty acids, and alpha-hydroxy acids as building block substrates. Andrimid is a NRP antibiotic that inhibits membrane biosynthesis by blocking bacterial acetyl coenzyme A carboxylases. It is synthesized in a hybrid NRPS-polyketide synthase (NRPS-PKS) using a fatty acid, phenylalanine, valine, and glycine. A remarkable feature of this synthetic system is that instead of a normal condensation domain, it uses two atypical free-standing proteins with homology to transglutaminases to catalyze the formation of the first and second amide bonds. We are characterizing the action of transglutaminase homologues (TGH) in andrimid synthesis using biochemical assays and X-ray crystallography. Initial investigations of the andrimid biosynthetic cluster found in Panteao agglomerans focused on the TGH, AdmF, which catalyzes the formation of the first amide bond. Crystallization trials have been initiated on AdmF in its apo form and in complex with its interacting binding partner, the peptide carrier protein domain AdmI. To date, only a few andrimid producing bacteria have been discovered. Using genome mining, a biosynthetic cluster homologous to the andrimid biosynthetic cluster found in Panteao agglomerans was identified in Vibrio coralliilyticus. The two TGHs, CoraF and CoraS, were cloned, expressed and purified, and crystallization trials are underway. Our progress in biochemical and biophysical characterization of AdmF, CoraF, and CoraS will be presented.
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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 | 0.000 |
| 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".