Evidence map›Paper›PMID 40339022›Full record

ArticleScience (New York, N.Y.)2025

De novo design of porphyrin-containing proteins as efficient and stereoselective catalysts.

Kaipeng Hou, Wei Huang, Miao Qi, Thomas H Tugwell, Turki M Alturaifi, Yuda Chen, Xingjie Zhang, Lei Lu, Samuel I Mann, Peng Liu and 2 more

Abstract read
In one paragraph

Article in Science (New York, N.Y.), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing 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

23 citing papers in PubMed.

  1. Terpene synthases screening in agarwood treeSynthetic and systems biotechnology · 2027
    Article
  2. Review
  3. High-throughput physics-based enzyme engineering.bioRxiv : the preprint server for biology · 2026
    Article
  4. Review
  5. Article
  6. Enantioselective Access to Trifluoromethylated Spirocyclopropyl Heterocycles.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Article
  7. Review
  8. AbioRxiv : the preprint server for biology · 2026
    Article
  9. Article
  10. Article
  11. bioRxiv : the preprint server for biology · 2026
    Article
  12. Review
  13. Review
  14. Article
  15. Article
  16. Article
  17. Article
  18. Protein engineering: status report.Protein engineering, design & selection : PEDS · 2026
    Review
  19. Article
  20. Review
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.

Kaipeng Hou *Department of Pharmaceutical Chemistry and Cardiovascular Research Institute, University of California, San Francisco, CA, USA.ORCID 0000-0002-4816-7067
Wei Huang *Department of Chemistry and Biochemistry, University of California Santa Barbara, Santa Barbara, CA , USA.ORCID 0009-0000-9476-8931
Miao Qi *Department of Pharmaceutical Chemistry and Cardiovascular Research Institute, University of California, San Francisco, CA, USA.ORCID 0000-0003-2232-8739
Thomas H TugwellDepartment of Chemistry, University of Pittsburgh, Pittsburgh, PA, USA.
Turki M AlturaifiDepartment of Chemistry, University of Pittsburgh, Pittsburgh, PA, USA.ORCID 0000-0002-6379-1669
Yuda ChenDepartment of Pharmaceutical Chemistry and Cardiovascular Research Institute, University of California, San Francisco, CA, USA.ORCID 0000-0002-5399-1720
Xingjie ZhangDepartment of Chemistry and Biochemistry, University of California Santa Barbara, Santa Barbara, CA , USA.
Lei LuDepartment of Pharmaceutical Chemistry and Cardiovascular Research Institute, University of California, San Francisco, CA, USA.ORCID 0000-0001-7097-1505
Samuel I MannDepartment of Pharmaceutical Chemistry and Cardiovascular Research Institute, University of California, San Francisco, CA, USA.ORCID 0000-0003-3392-3170
Peng LiuDepartment of Chemistry, University of Pittsburgh, Pittsburgh, PA, USA.ORCID 0000-0002-8188-632X
Yang YangDepartment of Chemistry and Biochemistry, University of California Santa Barbara, Santa Barbara, CA , USA.ORCID 0000-0002-4956-2034
William F DeGradoDepartment of Pharmaceutical Chemistry and Cardiovascular Research Institute, University of California, San Francisco, CA, USA.ORCID 0000-0003-4745-263X

Funding

User Training and OutreachP30GM124169 · NIGMS · UNIVERSITY OF CALIF-LAWRENC BERKELEY LAB · PI PAUL David ADAMS, Gregory L Hura · 2017 to 2026
$28.6M
Deciphering the relationship between structure, dynamics and function in helical bundle proteinsR35GM122603 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI WILLIAM DEGRADO · 2017 to 2026
$7.1M
Computational Models for Reactivity and Selectivity in Transition Metal-Catalyzed Olefin FunctionalizationR35GM128779 · NIGMS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Peng Liu · 2018 to 2026
$2.9M
De novo design of functional metallocofactor-binding proteinsR00GM143529 · NIGMS · UNIVERSITY OF CALIFORNIA RIVERSIDE · PI Samuel I Mann · 2024 to 2026
$747k
De novo design of functional metallocofactor-binding proteinsK99GM143529 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI MANN, SAMUEL I · 2021 to 2022
$188k
NIGMS NIH HHS K99 GM143529NIGMS NIH HHS P30 GM124169NIGMS NIH HHS R00 GM143529NIGMS NIH HHS R35 GM122603NIGMS NIH HHS R35 GM128779
6 · The paper itself

Abstract

De novo design of protein catalysts with high efficiency and stereoselectivity provides an attractive approach toward the design of environmentally benign catalysts. Here, we design proteins that incorporate histidine-ligated synthetic porphyrin and heme ligands. Four of 10 designed proteins catalyzed cyclopropanation with an enantiomeric ratio greater than 99:1. A second class of proteins were designed to catalyze a silicon-hydrogen insertion and were optimized by directed evolution in whole cells. The evolved proteins incorporated features unlikely to be generated by computational design alone, including a proline in an α helix. Molecular dynamics simulations showed that as the proteins evolved toward higher activity, their conformational ensembles narrowed to favor more productive conformations. Our work demonstrates that efficient de novo protein catalysts are designable and should be useful for manifold chemical processes.

Indexed as

CyclopropanesPorphyrinsProtein EngineeringProteinsCatalysisDirected Molecular EvolutionHemeHistidineHydrogenLigandsMethyltransferasesMolecular Dynamics SimulationProlineProtein ConformationSiliconStereoisomerismCyclopropanescyclopropane synthetaseHemeHistidineHydrogenLigandsMethyltransferasesPorphyrinsProlineProteinsSilicon

Identifiers

PMID40339022
PMCPMC12316402

What OpenQuestion holds

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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.