Evidence map›Paper›PMID 36569427›Full record

ArticleChem catalysis2022

Analysis of Laboratory-Evolved Flavin-Dependent Halogenases Affords a Computational Model for Predicting Halogenase Site Selectivity.

Mary C Andorfer, Declan Evans, Song Yang, Cyndi Qixin He, Anna M Girlich, Jaylie Vergara-Coll, Narayanasami Sukumar, K N Houk, Jared C Lewis

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Chem catalysis, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing 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

15 citing papers in PubMed.

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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

9 authors.

Mary C AndorferDepartment of Chemistry, University of Chicago, Chicago, IL 60637, USA.
Declan EvansDepartment of Chemistry and Biochemistry, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Song YangDepartment of Chemistry and Biochemistry, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Cyndi Qixin HeDepartment of Chemistry and Biochemistry, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Anna M GirlichDepartment of Chemistry, University of Chicago, Chicago, IL 60637, USA.
Jaylie Vergara-CollDepartment of Chemistry, University of Chicago, Chicago, IL 60637, USA.
Narayanasami SukumarNE-CAT and Department of Chemistry and Chemical Biology, Cornell University, Argonne National Laboratory, Building 436E, Argonne, IL 60439, USA.
K N HoukDepartment of Chemistry and Biochemistry, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Jared C LewisDepartment of Chemistry, Indiana University, Bloomington, IN 47405, USA.

Funding

User Training and OutreachP30GM124165 · NIGMS · CORNELL UNIVERSITY · PI MALCOLM S. CAPEL · 2018 to 2026
$34.2M
CHEMISTRY BIOLOGY INTERFACE TRAINING PROGRAMT32GM008496 · NIGMS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI MAYNARD, HEATHER D · 1993 to 2019
$6.3M
Predoctoral Training Program in Chemistry & BiologyT32GM008720 · NIGMS · UNIVERSITY OF CHICAGO · PI PICCIRILLI, JOSEPH ANTHONY · 1999 to 2020
$4.7M
Directed Evolution of Halogenases For Small Molecule FunctionalizationR01GM115665 · NIGMS · UNIVERSITY OF CHICAGO · PI LEWIS, JARED C · 2015 to 2022
$2.5M
Pixel Array Detector for Macromolecular CrystallographyS10OD021527 · OD · CORNELL UNIVERSITY · PI EALICK, STEVEN E · 2016 to 2016
$2.0M
NIGMS NIH HHS P30 GM124165NIGMS NIH HHS R01 GM115665NIGMS NIH HHS T32 GM008496NIGMS NIH HHS T32 GM008720NIH HHS S10 OD021527
6 · The paper itself

Abstract

Flavin-dependent halogenases (FDHs) catalyze selective halogenation of electron-rich aromatic compounds without the need for harsh oxidants required by conventional oxidative halogenation reactions. Predictive models for halogenase site selectivity could greatly improve their utility for chemical synthesis. Toward this end, we analyzed the structures and selectivity of three halogenase variants evolved to halogenate tryptamine with orthogonal selectivity. Crystal structures and reversion mutations revealed key residues involved in altering halogenase selectivity. Density functional theory calculations and molecular dynamics simulations are both consistent with hypohalous acid as the active halogenating species in FDH catalysis. This model was used to accurately predict the site selectivity of halogenase variants toward different synthetic substrates, providing a valuable tool for implementing halogenases in biocatalysis efforts.

Indexed as

C-H functionalizationdirected evolutionhalogenasesite-selective

Identifiers

PMID36569427
PMCPMC9784200

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Registered trials

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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.