Evidence map›Paper›PMID 29461523›Full record

ArticleNature chemistry2018

Evolving artificial metalloenzymes via random mutagenesis.

Hao Yang, Alan M Swartz, Hyun June Park, Poonam Srivastava, Ken Ellis-Guardiola, David M Upp, Gihoon Lee, Ketaki Belsare, Yifan Gu, Chen Zhang and 2 more

Abstract read
In one paragraph

Article in Nature chemistry, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.

0numbers the graph read from it
0cells of the map it votes in
42citing 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

42 citing papers in PubMed.

  1. Review
  2. Reprogramming NAD(P)Angewandte Chemie (International ed. in English) · 2026
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  4. Chemical neighborhood exploration for substrate discovery in biocatalysis.Proceedings of the National Academy of Sciences of the United States of America · 2026
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  7. Identification of Laccase Family ofInternational journal of molecular sciences · 2024
    Article
  8. Review
  9. Article
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  11. Review
  12. Article
  13. Review
  14. Article
  15. Article
  16. First and second sphere interactions accelerate non-nativeChemical communications (Cambridge, England) · 2023
    Article
  17. Review
  18. Article
  19. Review
  20. 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

12 authors.

Hao YangMerck Research Laboratories, 126 E. Lincoln Avenue, Rahway, New Jersey 07065, USA.
Alan M SwartzDepartment of Chemistry, University of Chicago, 5735 S. Ellis Avenue, Chicago, Illinois 60637, USA.
Hyun June ParkDepartment of Chemistry, University of Chicago, 5735 S. Ellis Avenue, Chicago, Illinois 60637, USA.
Poonam SrivastavaCargill, Inc., 14800 28th Avenue N, Plymouth, Minnesota 55447, USA.
Ken Ellis-GuardiolaDepartment of Chemistry, University of Chicago, 5735 S. Ellis Avenue, Chicago, Illinois 60637, USA.
David M UppDepartment of Chemistry, University of Chicago, 5735 S. Ellis Avenue, Chicago, Illinois 60637, USA.
Gihoon LeeDepartment of Chemistry, University of Chicago, 5735 S. Ellis Avenue, Chicago, Illinois 60637, USA.
Ketaki BelsareDepartment of Chemistry, University of Chicago, 5735 S. Ellis Avenue, Chicago, Illinois 60637, USA.
Yifan GuDepartment of Chemistry, University of Chicago, 5735 S. Ellis Avenue, Chicago, Illinois 60637, USA.
Chen ZhangProvivi, Inc., 1701 Colorado Avenue, Santa Monica, California 90404, USA.
Raymond E MoelleringDepartment of Chemistry, University of Chicago, 5735 S. Ellis Avenue, Chicago, Illinois 60637, USA.ORCID 0000-0002-2043-7838
Jared C LewisDepartment of Chemistry, University of Chicago, 5735 S. Ellis Avenue, Chicago, Illinois 60637, USA.ORCID 0000-0003-2800-8330

Funding

Predoctoral Training Program in Chemistry & BiologyT32GM008720 · NIGMS · UNIVERSITY OF CHICAGO · PI PICCIRILLI, JOSEPH ANTHONY · 1999 to 2020
$4.7M
Targeting Transcription with Synthetic BiologicsDP2GM128199 · NIGMS · UNIVERSITY OF CHICAGO · PI MOELLERING, RAYMOND E · 2017 to 2017
$2.3M
Distribution, regulation and function of a novel lysine PTM in metabolic diseaseR00CA175399 · NCI · UNIVERSITY OF CHICAGO · PI MOELLERING, RAYMOND E · 2015 to 2017
$712k
NCI NIH HHS R00 CA175399NIGMS NIH HHS DP2 GM128199NIGMS NIH HHS T32 GM008720
6 · The paper itself

Abstract

Random mutagenesis has the potential to optimize the efficiency and selectivity of protein catalysts without requiring detailed knowledge of protein structure; however, introducing synthetic metal cofactors complicates the expression and screening of enzyme libraries, and activity arising from free cofactor must be eliminated. Here we report an efficient platform to create and screen libraries of artificial metalloenzymes (ArMs) via random mutagenesis, which we use to evolve highly selective dirhodium cyclopropanases. Error-prone PCR and combinatorial codon mutagenesis enabled multiplexed analysis of random mutations, including at sites distal to the putative ArM active site that are difficult to identify using targeted mutagenesis approaches. Variants that exhibited significantly improved selectivity for each of the cyclopropane product enantiomers were identified, and higher activity than previously reported ArM cyclopropanases obtained via targeted mutagenesis was also observed. This improved selectivity carried over to other dirhodium-catalysed transformations, including N-H, S-H and Si-H insertion, demonstrating that ArMs evolved for one reaction can serve as starting points to evolve catalysts for others.

Indexed as

MutagenesisBiocatalysisMetalloproteinsMolecular StructurePolymerase Chain ReactionMetalloproteins

Identifiers

PMID29461523
PMCPMC5891097

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.