Biochemical and biophysical investigation of the HalM2 lanthipeptide synthetase using mass spectrometry
Bibliographic record
Abstract
The rapid emergence of antimicrobial resistance in clinical settings has called for renewed efforts to discover and develop new antimicrobial compounds. Lanthipeptides present a promising, genetically encoded molecular scaffold for the engineering of structurally complex, biologically active peptides. These peptide natural products are constructed by enzymes (lanthipeptide synthetases) with relaxed substrate specificity that iteratively modify the precursor lanthipeptide to generate structures with defined sets of thioether macrocycles. The mechanistic features that guide the maturation of lanthipeptides into their proper, fully modified forms are obscured by the complexity of the multistep maturation and the large size and dynamic structures of the synthetases and precursor peptides. Over the past several years, our lab has been developing a suite of mass spectrometry-based techniques that are ideally suited to untangling the complex reaction sequences and molecular interactions that define lanthipeptide biosynthesis. This review focuses on our development and application of these mass spectrometry-based techniques to investigate the biochemical, kinetic, and biophysical properties of the haloduracin β class II lanthipeptide synthetase, HalM2.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| 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 source (direct Gemma or distilled Codex), 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".