Discovery and mechanistic study of coral-derived terpene synthases reveal insights into terpene scaffolds' orthologous evolution
Bibliographic record
Abstract
Marine corals, rich in diverse terpenoids, are a promising resource for drug discovery, yet their potential is hindered by low supply. Recent reports on coral-derived terpene synthases (TSs) have confirmed that corals are indeed the primary producers of coral terpenoids, pointing us towards a solution for the low supply issue. However, only a few coral TSs have been functionally identified, lacking comprehensive studies on their mechanisms, phylogenetic relationships, and engineering applications. To address these gaps, we conducted genome mining to discover and study all TSs within the genome of the sea whip coral, Paramuricea clavata. We performed isotope labeling, protein crystallography, and quantum mechanics/molecular mechanics (QM/MM) calculations-guided mutations, particularly focusing on a biflorane synthase, PcTS1. These multifaceted experiments have elucidated the catalytic mechanisms of PcTS1 in detail. Furthermore, our phylogenetic analysis of coral TSs, which are crucial for the biosynthesis of structurally related terpene skeletons such as biflorane, eunicellane, and cembrane, has provided significant insights into the evolutionary development of terpene scaffolds. Based on these insights, we have applied evolution-based engineering efforts to PcTS1, successfully producing new terpene structures that are related to its mechanistic intermediates. This research not only establishes a connection between the chemical diversity of terpenes and coral genomes but also enhances our understanding of coral TSs from both mechanistic and evolutionary perspectives. In addition, this work offers a new research paradigm for the study of coral-derived terpenoids and inspires future high-quality coral sequencing efforts.
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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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 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".