Thioesterase from Cereulide Biosynthesis Is Responsible for Oligomerization and Macrocyclization of a Linear Tetradepsipeptide
Bibliographic record
Abstract
Cereulide is a toxic cyclic depsidodecapeptide produced in Bacillus cereus by two nonribosomal peptide synthetases, CesA and CesB. While highly similar in structure to valinomycin and with a homologous biosynthetic gene cluster, recent work suggests that cereulide is produced via a different mechanism that relies on a noncanonical coupling of two didepsipeptide-peptidyl carrier protein (PCP) bound intermediates. Ultimately this alternative mechanism generates a tetradepsipeptide-PCP bound intermediate that differs from the tetradepsipeptide-PCP intermediate predicted from canonical activity of CesA and CesB. To differentiate between the mechanisms, both tetradepsipeptides were prepared as N -acetyl cysteamine thioesters (SNAC), and the ability of the purified recombinant terminal CesB thioesterase (CesB TE) to oligomerize and macrocyclize each substrate was probed. Only the canonical substrate is converted to cereulide, ruling out the alternative mechanism. It was demonstrated that CesB TE can use related tetradepsipeptide substrates, such as the valinomycin tetradespipetide and a hybrid cereulide–valinomycin tetradepsipetide in conjunction with its native substrate to generate chimeric natural products. This work clarifies the biosynthetic origins of cereulide and provides a powerful biocatalyst to access analogues of these ionophoric natural products.
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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) | 0.001 | 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) | 0.001 | 0.001 |
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".