Evidence map›Paper›PMID 34075034›Full record

ArticleNature communications2021

Flavin-dependent halogenases catalyze enantioselective olefin halocyclization.

Dibyendu Mondal, Brian F Fisher, Yuhua Jiang, Jared C Lewis

Abstract read
In one paragraph

Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing 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

19 citing papers in PubMed.

  1. Article
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  11. Naturally Occurring Organohalogen Compounds-A Comprehensive Review.Progress in the chemistry of organic natural products · 2023
    Review
  12. Article
  13. Article
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  15. Article
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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

4 authors.

Dibyendu MondalDepartment of Chemistry, Indiana University, Bloomington, IN, 47405, USA.ORCID 0000-0003-0255-5029
Brian F FisherDepartment of Chemistry, Indiana University, Bloomington, IN, 47405, USA.ORCID 0000-0003-1727-2494
Yuhua JiangDepartment of Chemistry, Indiana University, Bloomington, IN, 47405, USA.
Jared C LewisDepartment of Chemistry, Indiana University, Bloomington, IN, 47405, USA. jcl3@iu.edu.ORCID 0000-0003-2800-8330

Funding

Directed Evolution of Halogenases For Small Molecule FunctionalizationR01GM115665 · NIGMS · UNIVERSITY OF CHICAGO · PI LEWIS, JARED C · 2015 to 2022
$2.5M
Expanding the substrate scope of flavin-dependent halogenase biocatalysts to electron-deficient arenes and resveratrol oligomersF32GM123693 · NIGMS · UNIVERSITY OF CHICAGO · PI FISHER, BRIAN FRANCIS · 2017 to 2019
$164k
NIGMS NIH HHS F32 GM123693NIGMS NIH HHS R01 GM115665
6 · The paper itself

Abstract

Halocyclization of alkenes is a powerful bond-forming tool in synthetic organic chemistry and a key step in natural product biosynthesis, but catalyzing halocyclization with high enantioselectivity remains a challenging task. Identifying suitable enzymes that catalyze enantioselective halocyclization of simple olefins would therefore have significant synthetic value. Flavin-dependent halogenases (FDHs) catalyze halogenation of arene and enol(ate) substrates. Herein, we reveal that FDHs engineered to catalyze site-selective aromatic halogenation also catalyze non-native bromolactonization of olefins with high enantioselectivity and near-native catalytic proficiency. Highly selective halocyclization is achieved by characterizing and mitigating the release of HOBr from the FDH active site using a combination of reaction optimization and protein engineering. The structural origins of improvements imparted by mutations responsible for the emergence of halocyclase activity are discussed. This expansion of FDH catalytic activity presages the development of a wide range of biocatalytic halogenation reactions.

Indexed as

BiocatalysisAlkenesCatalytic DomainCyclizationEnzyme AssaysFlavinsHalogenationKineticsMolecular Docking SimulationMutagenesisMutationOxidoreductasesProtein EngineeringStereoisomerismAlkenesFlavinsOxidoreductasestryptophan halogenase

Identifiers

PMID34075034
PMCPMC8169660

What OpenQuestion holds

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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.