Evidence map›Paper›PMID 30270109›Full record

ArticleMolecular cell2018

Automated Design of Efficient and Functionally Diverse Enzyme Repertoires.

Olga Khersonsky, Rosalie Lipsh, Ziv Avizemer, Yacov Ashani, Moshe Goldsmith, Haim Leader, Orly Dym, Shelly Rogotner, Devin L Trudeau, Jaime Prilusky and 4 more

Abstract read
In one paragraph

Article in Molecular cell, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 123 papers.

0numbers the graph read from it
0cells of the map it votes in
123citing 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

123 citing papers in PubMed.

  1. Review
  2. Article
  3. Article
  4. Review
  5. Review
  6. Article
  7. Applications and limitations of AI tools in enzyme design.Protein science : a publication of the Protein Society · 2026
    Review
  8. Empowering Precision C-H Functionalization: Advances in Peroxygenase Engineering.Angewandte Chemie (International ed. in English) · 2026
    Review
  9. Promiscuity-Guided Enzyme Evolution via Substrate Multiplexed Screening.Angewandte Chemie (International ed. in English) · 2026
    Review
  10. Substrate scope of ancestral versus modern family-1 glycosidases.Protein science : a publication of the Protein Society · 2026
    Article
  11. Chemical neighborhood exploration for substrate discovery in biocatalysis.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  12. Review
  13. Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. Protein engineering: status report.Protein engineering, design & selection : PEDS · 2026
    Review
  19. Article
  20. Glycosylated cannabinoids meet computational enzyme design.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article

63 more citing papers are in PubMed but not listed here.

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

14 authors.

Olga KhersonskyDepartment of Biomolecular Sciences, Weizmann Institute of Science, Rehovot 7610001, Israel.
Rosalie LipshDepartment of Biomolecular Sciences, Weizmann Institute of Science, Rehovot 7610001, Israel.
Ziv AvizemerDepartment of Biomolecular Sciences, Weizmann Institute of Science, Rehovot 7610001, Israel.
Yacov AshaniDepartment of Biomolecular Sciences, Weizmann Institute of Science, Rehovot 7610001, Israel.
Moshe GoldsmithDepartment of Biomolecular Sciences, Weizmann Institute of Science, Rehovot 7610001, Israel.
Haim LeaderDepartment of Biomolecular Sciences, Weizmann Institute of Science, Rehovot 7610001, Israel.
Orly DymIsrael Structural Proteomics Center, Weizmann Institute of Science, Rehovot 7610001, Israel.
Shelly RogotnerIsrael Structural Proteomics Center, Weizmann Institute of Science, Rehovot 7610001, Israel.
Devin L TrudeauDepartment of Biomolecular Sciences, Weizmann Institute of Science, Rehovot 7610001, Israel.
Jaime PriluskyBioinformatics and Biological Computing Unit, Weizmann Institute of Science, Rehovot 7610001, Israel.
Pep Amengual-RigoBarcelona Supercomputing Center, Jordi Girona 31, 08034 Barcelona, Spain.
Victor GuallarBarcelona Supercomputing Center, Jordi Girona 31, 08034 Barcelona, Spain; ICREA, Passeig Lluís Companys 23, 08010 Barcelona, Spain.
Dan S TawfikDepartment of Biomolecular Sciences, Weizmann Institute of Science, Rehovot 7610001, Israel.
Sarel J FleishmanDepartment of Biomolecular Sciences, Weizmann Institute of Science, Rehovot 7610001, Israel. Electronic address: sarel.fleishman@weizmann.ac.il.

Funding

European Research Council 335439
6 · The paper itself

Abstract

Substantial improvements in enzyme activity demand multiple mutations at spatially proximal positions in the active site. Such mutations, however, often exhibit unpredictable epistatic (non-additive) effects on activity. Here we describe FuncLib, an automated method for designing multipoint mutations at enzyme active sites using phylogenetic analysis and Rosetta design calculations. We applied FuncLib to two unrelated enzymes, a phosphotriesterase and an acetyl-CoA synthetase. All designs were active, and most showed activity profiles that significantly differed from the wild-type and from one another. Several dozen designs with only 3-6 active-site mutations exhibited 10- to 4,000-fold higher efficiencies with a range of alternative substrates, including hydrolysis of the toxic organophosphate nerve agents soman and cyclosarin and synthesis of butyryl-CoA. FuncLib is implemented as a web server (http://FuncLib.weizmann.ac.il); it circumvents iterative, high-throughput experimental screens and opens the way to designing highly efficient and diverse catalytic repertoires.

Indexed as

Catalytic DomainProtein EngineeringAcyl Coenzyme ACatalysisCoenzyme A LigasesKineticsMutationOrganophosphorus CompoundsPhosphoric Triester HydrolasesPhylogenySoftwareSubstrate Specificityacetate-CoA ligase (ADP-forming)Acyl Coenzyme Abutyryl-coenzyme ACoenzyme A Ligasescyclohexyl methylphosphonofluoridateOrganophosphorus CompoundsPhosphoric Triester Hydrolasesenzyme designenzyme repertoiresepistatic mutationsFuncLibnerve agentsPROSSRosetta

Identifiers

PMID30270109
PMCPMC6193528

What OpenQuestion holds

Textmetadata
LicenceTDM
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.