Evidence map›Paper›PMID 33300646›Full record

ArticleAngewandte Chemie (International ed. in English)2021

Engineered Enzymes Enable Selective N-Alkylation of Pyrazoles With Simple Haloalkanes.

Ludwig L Bengel, Benjamin Aberle, Alexander-N Egler-Kemmerer, Samuel Kienzle, Bernhard Hauer, Stephan C Hammer

Open access · hybridAbstract read
In one paragraph

Article in Angewandte Chemie (International ed. in English), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed
5.5field-weighted citation impact, top 3% of its field
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

32 citing papers in PubMed, 95 citations in OpenAlex.

  1. Article
  2. Shape-Conserving Atom Replacements.Chemical reviews · 2026
    Review
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  5. A Riboflavin-Derived Flavinium Salt Mediates Chemoselective Methylation Reactions.Chemistry (Weinheim an der Bergstrasse, Germany) · 2026
    Article
  6. Article
  7. Review
  8. Article
  9. Article
  10. Article
  11. An Update: Enzymatic Synthesis for Industrial Applications.Angewandte Chemie (International ed. in English) · 2025
    Review
  12. Article
  13. Article
  14. Addressing epistasis in the design of protein function.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  15. Review
  16. Article
  17. Review
  18. 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

6 authors at 1 institution in 1 country.

Ludwig L BengelDepartment of Technical Biochemistry, Institute of Biochemistry and Technical Biochemistry, University of Stuttgart, Allmandring 31, 70569, Stuttgart, Germany.ORCID 0000-0003-0069-1051
Benjamin AberleDepartment of Technical Biochemistry, Institute of Biochemistry and Technical Biochemistry, University of Stuttgart, Allmandring 31, 70569, Stuttgart, Germany.ORCID 0000-0002-1649-0425
Alexander-N Egler-KemmererDepartment of Technical Biochemistry, Institute of Biochemistry and Technical Biochemistry, University of Stuttgart, Allmandring 31, 70569, Stuttgart, Germany.ORCID 0000-0002-8976-8977
Samuel KienzleDepartment of Technical Biochemistry, Institute of Biochemistry and Technical Biochemistry, University of Stuttgart, Allmandring 31, 70569, Stuttgart, Germany.ORCID 0000-0002-6816-0401
Bernhard HauerDepartment of Technical Biochemistry, Institute of Biochemistry and Technical Biochemistry, University of Stuttgart, Allmandring 31, 70569, Stuttgart, Germany.ORCID 0000-0001-6259-3348
Stephan C HammerFaculty of Chemistry, Organic Chemistry and Biocatalysis, Bielefeld University, Universitätsstraße 25, 33615, Bielefeld, Germany.ORCID 0000-0002-3620-9362
University of Stuttgart · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Selective alkylation of pyrazoles could solve a challenge in chemistry and streamline synthesis of important molecules. Here we report catalyst-controlled pyrazole alkylation by a cyclic two-enzyme cascade. In this enzymatic system, a promiscuous enzyme uses haloalkanes as precursors to generate non-natural analogs of the common cosubstrate S-adenosyl-l-methionine. A second engineered enzyme transfers the alkyl group in highly selective C-N bond formations to the pyrazole substrate. The cosubstrate is recycled and only used in catalytic amounts. Key is a computational enzyme-library design tool that converted a promiscuous methyltransferase into a small enzyme family of pyrazole-alkylating enzymes in one round of mutagenesis and screening. With this enzymatic system, pyrazole alkylation (methylation, ethylation, propylation) was achieved with unprecedented regioselectivity (>99 %), regiodivergence, and in a first example on preparative scale.

Indexed as

Alkyl and Aryl TransferasesAlkylationAspergillusFungal ProteinsHumansHydrocarbons, HalogenatedMethyltransferasesProof of Concept StudyProtein EngineeringPyrazolesSubstrate SpecificityAlkyl and Aryl TransferasesFungal ProteinsHydrocarbons, HalogenatedMethyltransferasesPyrazolesalkylationbiocatalysisenzyme cofactorsenzyme engineeringpyrazoles

Identifiers

PMID33300646
PMCPMC7986378
OpenAlexW3112282093

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.