Engineering of the UGT86C11 Glycosyltransferase for Improving Catalytic Efficiency and Efficient Biosynthesis of Neoandrographolide
Why this work is in the frame
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Bibliographic record
Abstract
High Resolution Image Download MS PowerPoint Slide Neoandrographolide is a bioactive diterpenoid biosynthesized in the medicinal plant Andrographis paniculata by the C 19 - O -glycosyltransferase UGT86C11. Neoandrographolide supply typically suffers owing to its inadequate amounts in A. paniculata, highlighting the need for an efficient bioprocess to produce this compound. We combined computational modeling of UGT86C11 structure and diterpenoid binding dynamics with site-directed mutagenesis and developed UGT86C11 variants (E163A, T403A, and F404A) exhibiting ∼2-fold increased catalytic efficiency. E163A, T403A, and F404A displayed increased turnover of the C 19 - O -glycosylation reaction. Moreover, T403A and F404A showed higher affinity for the UDP-glucose sugar donor. Escherichia coli expression of UGT86C11 variants, coupled with an improved UDP-glucose regeneration system, enabled a remarkable biotransformation rate of neoandrographolide, reaching up to 91% conversion as compared to ∼45% using native UGT86C11. Besides, UGT86C11 variants demonstrated ∼6-fold higher neoandrographolide biosynthesis in Nicotiana benthamiana . Thus, the engineered UGT86C11 presents a promising avenue for the efficient production of neoandrographolide using both plant and microbial hosts.
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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 it