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Record W4283077391 · doi:10.21203/rs.3.rs-1759048/v1

P450cam (CYP101A1) Mutants for Endosulfan Degradation: Complete Dehalogenation of Endosulfan Diol and Related Compounds

2022· preprint· en· W4283077391 on OpenAlexafffund
Abdul Rehman, Nicole Gkaleni, Priyadarshini Balaraman, Brinda Prasad, Erika Plettner

Bibliographic record

VenueResearch Square · 2022
Typepreprint
Languageen
FieldPharmacology, Toxicology and Pharmaceutics
TopicPharmacogenetics and Drug Metabolism
Canadian institutionsSimon Fraser University
FundersNatural Sciences and Engineering Research Council of CanadaSimon Fraser University
KeywordsChemistryDiolStereochemistryEndosulfanBicyclic moleculeHalogenationDihydroxylationOrganic chemistryEtherMedicinal chemistryCatalysisPesticideEnantioselective synthesis

Abstract

fetched live from OpenAlex

Abstract Cytochrome P450cam (CYP101A1) from the soil bacterium Pseudomonas putida oxidizes camphor regio- and stereoselectively at the 5-position, to give 5-exo-hydroxycamphor. Previously, we randomly mutated P450cam and selected seven mutants on the bicyclic polychlorinated insecticide and persistent organic pollutant, endosulfan (ES). Here we describe the activity of the seven mutants of P450cam with ES diol, ES, ES lactone, ES ether, ES sulfate, and heptachlor. ES diol, ES lactone, ES ether, and ES sulfate are persistent biotransformation products of ES in the environment. They all have the hexachlorinated norbornene (bicyclo[2.2.1] hept-2-ene) moiety intact. The P450cam mutants (and to a small extent the wild type) convert these substrates to substituted ortho-quinones, which we detected using 4-aminoantipyrine (4-AAP) in spectrophotometric assays. Here we have studied dehalogenation of ES and related compounds catalyzed by the endosulfan–selected P450cam mutants, using in vitro kinetics, chloride release assays, and 13C labeled endosulfan diol. We found that mutants ES7 (V247F/D297N/K314E) and ES6 (G120S) were significantly more active towards ES diol than the WT. On average, close to six Cl- ions are released per aromatic product detected upon turnover of ES diol. Finally, product isolation from reactions with non-labeled and 13C labeled ES diol confirmed that substituted catechols formed. Based on these findings, we propose that dehalogenagion begins with the oxidation of the ES double bond on the norbornene system, proceeds with eliminating six chloride ions and loss of the bridge as CO2 to furnish an ortho-quinone, which can be reduced non-enzymatically to the corresponding catechol.

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 machine prediction

Teacher imitation

Not 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.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation 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 score0.003
Threshold uncertainty score0.005

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0010.001

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.

Opus teacher head0.317
GPT teacher head0.533
Teacher spread0.216 · 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 source (direct Gemma or distilled Codex), 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

Citations2
Published2022
Admission routes2
Has abstractyes

Explore more

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