Evidence map›Paper›PMID 42332020›Full record

ArticleNature chemical biology2026

Discovery of noncanonical cytochrome P450 enzymes in nature.

Andy K L Nguy, Kendra A Ireland, Chase M Kayrouz, Juan Carlos Cáceres, Jonathan Z Huang, Vanessa Y Ying, Joanna A Quaye, Brandon L Greene, Katherine M Davis, Mohammad R Seyedsayamdost

Abstract read
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Article in Nature chemical biology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Design-Evolution Synergy Enables New-to-Nature Enzyme Chemistry.bioRxiv : the preprint server for biology · 2026
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors.

Andy K L Nguy *Department of Chemistry, Princeton University, Princeton, NJ, USA.
Kendra A Ireland *Department of Chemistry, Emory University, Atlanta, GA, USA.
Chase M Kayrouz *Department of Chemistry, Princeton University, Princeton, NJ, USA.ORCID http://orcid.org/0000-0001-6754-422X
Juan Carlos CáceresInterdisciplinary Program in Quantitative Biosciences, University of California, Santa Barbara, Santa Barbara, CA, USA.ORCID http://orcid.org/0000-0003-2458-8243
Jonathan Z HuangDepartment of Chemistry, Princeton University, Princeton, NJ, USA.
Vanessa Y YingDepartment of Chemistry, Princeton University, Princeton, NJ, USA.
Joanna A QuayeDepartment of Chemistry, Princeton University, Princeton, NJ, USA.ORCID http://orcid.org/0000-0002-7041-4570
Brandon L GreeneInterdisciplinary Program in Quantitative Biosciences, University of California, Santa Barbara, Santa Barbara, CA, USA.
Katherine M DavisDepartment of Chemistry, Emory University, Atlanta, GA, USA.ORCID http://orcid.org/0000-0002-0258-8907
Mohammad R SeyedsayamdostDepartment of Chemistry, Princeton University, Princeton, NJ, USA. mrseyed@princeton.edu.ORCID http://orcid.org/0000-0003-2707-4854

Funding

Unraveling the dynamics that enable unusual heme enzyme reactivityR35GM147557 · NIGMS · EMORY UNIVERSITY · PI Katherine Marie Davis · 2022 to 2026
$1.9M
From Genes to Molecules and Back: Expanding the Chemical Space of Microbial and Microbiome Natural ProductsR35GM152049 · NIGMS · PRINCETON UNIVERSITY · PI Mohammad R Seyedsayamdost · 2024 to 2026
$1.2M
Regulation and maintenance of thiyl radicals in enzyme catalysis and protein degradationR35GM154993 · NIGMS · UNIVERSITY OF CALIFORNIA SANTA BARBARA · PI Brandon Greene · 2024 to 2026
$1.1M
Life Sciences Research Foundation (LSRF) Postdoctoral Fellowship sponsored by the Open Philanthropy ProjectNational Science Foundation (NSF) GRFP No. 1937971NIGMS NIH HHS R35 GM147557NIGMS NIH HHS R35 GM152049NIGMS NIH HHS R35 GM154993U.S. Department of Health & Human Services | National Institutes of Health (NIH) R35 GM147557U.S. Department of Health & Human Services | National Institutes of Health (NIH) R35 GM152049U.S. Department of Health & Human Services | National Institutes of Health (NIH) R35 GM154993
6 · The paper itself

Abstract

Cytochrome P450s (CYPs) constitute a superfamily of thiolate-ligated heme metalloenzymes principally responsible for the hydroxylation of unactivated C-H bonds. The proximal cysteine is an obligatory and universally conserved residue for the CYP enzyme class. Herein, we challenge this paradigm by systematically identifying noncanonical CYPs (ncCYPs) that do not harbor a proximal cysteine ligand. Our bioinformatic search revealed 20 distinct ncCYP families encoded in diverse microbial genomes with alternative residues at this position. We characterize a native serine-ligated CYP with a high-spin ferric resting state that catalyzes azide reduction and nitrene insertion reactions. Its crystal structure clearly shows a typical CYP fold and a serine alkoxide as a proximal heme ligand. In addition, we report the discovery and characterization of the first native selenocysteine-ligated CYP in nature. Our findings expand the CYP metalloenzyme family and provide opportunities for future enzymatic and biocatalytic discoveries.

Indexed as

Cytochrome P-450 Enzyme SystemBiocatalysisCrystallography, X-RayModels, MolecularCytochrome P-450 Enzyme System

Identifiers

PMID42332020

What OpenQuestion holds

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.