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Record W2519223696 · doi:10.1038/srep33099

Molecular evolutionary dynamics of cytochrome P450 monooxygenases across kingdoms: Special focus on mycobacterial P450s

2016· article· en· W2519223696 on OpenAlexafffund
Mohammad Khalid Parvez, Lehlohonolo Benedict Qhanya, Ntsane Trevor Mthakathi, Ipeleng Kopano Rosinah Kgosiemang, Hans Denis Bamal, Nataraj Sekhar Pagadala, Ting Xie, Haoran Yang, Hengye Chen, Chrispian W. Theron, Richie Monyaki, Seiso Caiphus Raselemane, Vuyani Salewe, Bogadi Lorato Mongale, Retshedisitswe Godfrey Matowane, Sara Mohamed Hasaan Abdalla, Wool Isaac Booi, Mari van Wyk, Dedré Olivier, Charlotte E. Boucher, David R. Nelson, Jack A. Tuszyński, Jonathan M. Blackburn, Jae‐Hyuk Yu, Samson S. Mashele, Wanping Chen, Khajamohiddin Syed

Bibliographic record

VenueScientific Reports · 2016
Typearticle
Languageen
FieldPharmacology, Toxicology and Pharmaceutics
TopicPharmacogenetics and Drug Metabolism
Canadian institutionsUniversity of Alberta
FundersNatural Sciences and Engineering Research Council of CanadaDepartment of Higher Education and TrainingMinistry of Science, ICT and Future PlanningCentral University of TechnologyAllard FoundationNational Research FoundationUniversity of Wisconsin-Madison
KeywordsMonooxygenaseBiologyCytochrome P450Phylogenetic treeFunction (biology)GenomeEvolutionary biologyMolecular evolutionComputational biologyGeneticsFunctional diversityGeneEcologyBiochemistryEnzyme

Abstract

fetched live from OpenAlex

Since the initial identification of cytochrome P450 monooxygenases (CYPs/P450s), great progress has been made in understanding their structure-function relationship, diversity and application in producing compounds beneficial to humans. However, the molecular evolution of P450s in terms of their dynamics both at protein and DNA levels and functional conservation across kingdoms still needs investigation. In this study, we analyzed 17 598 P450s belonging to 113 P450 families (bacteria -42; fungi -19; plant -28; animal -22; plant and animal -1 and common P450 family -1) and found highly conserved and rapidly evolving P450 families. Results suggested that bacterial P450s, particularly P450s belonging to mycobacteria, are highly conserved both at protein and DNA levels. Mycobacteria possess the highest P450 diversity percentage compared to other microbes and have a high coverage of P450s (≥1%) in their genomes, as found in fungi and plants. Phylogenetic and functional analyses revealed the functional conservation of P450s despite belonging to different biological kingdoms, suggesting the adherence of P450s to their innate function such as their involvement in either generation or oxidation of steroids and structurally related molecules, fatty acids and terpenoids. This study's results offer new understanding of the dynamic structural nature of P450s.

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)0.002
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesMeta-epidemiology (narrow), Insufficient payload (model declined to judge)
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 score0.201
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0020.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.001
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0020.000

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 head0.048
GPT teacher head0.384
Teacher spread0.335 · 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.

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

Citations84
Published2016
Admission routes2
Has abstractyes

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