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Record W4319161056 · doi:10.3389/fpls.2023.1125158

Discovery of a cytochrome P450 enzyme catalyzing the formation of spirooxindole alkaloid scaffold

2023· article· en· W4319161056 on OpenAlexafffund
Tuan‐Anh Minh Nguyen, Dagny Grzech, Khoa Chung, Zhicheng Xia, Trinh‐Don Nguyen, Thu‐Thuy T. Dang

Bibliographic record

VenueFrontiers in Plant Science · 2023
Typearticle
Languageen
FieldPharmacology, Toxicology and Pharmaceutics
TopicAlkaloids: synthesis and pharmacology
Canadian institutionsUniversity of British Columbia, Okanagan CampusUniversity of British Columbia
FundersNatural Sciences and Engineering Research Council of CanadaUniversity of British ColumbiaMichael Smith Health Research BCLeibniz-GemeinschaftCanada Foundation for Innovation
KeywordsPharmacophoreChemistrySaccharomyces cerevisiaeEnzymeOxindoleDrug discoveryAlkaloidScaffoldBiochemistryMoietyCytochrome P450YeastStereochemistryCatalysisComputer science

Abstract

fetched live from OpenAlex

Spirooxindole alkaloids feature a unique scaffold of an oxindole ring sharing an atom with a heterocyclic moiety. These compounds display an extensive range of biological activities such as anticancer, antibiotics, and anti-hypertension. Despite their structural and functional significance, the establishment and rationale of the spirooxindole scaffold biosynthesis are yet to be elucidated. Herein, we report the discovery and characterization of a cytochrome P450 enzyme from kratom ( Mitragyna speciosa ) responsible for the formation of the spirooxindole alkaloids 3- epi -corynoxeine (3 R , 7 R ) and isocorynoxeine (3 S , 7 S ) from the corynanthe-type (3 R )-secoyohimbane precursors. Expression of the newly discovered enzyme in Saccharomyces cerevisiae yeast allows for the efficient in vivo and in vitro production of spirooxindoles. This discovery highlights the versatility of plant cytochrome P450 enzymes in building unusual alkaloid scaffolds and opens a gateway to access the prestigious spirooxindole pharmacophore and its derivatives.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not 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.

metaresearch head score (Codex)0.003
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.064
Threshold uncertainty score0.513

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0030.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0010.002
Science and technology studies0.0000.001
Scholarly communication0.0000.001
Open science0.0010.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

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.

Opus teacher head0.065
GPT teacher head0.362
Teacher spread0.297 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

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".

Quick stats

Citations32
Published2023
Admission routes2
Has abstractyes

Explore more

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