Evidence map›Paper›PMID 41768769›Full record

ArticleACS central science2026

Directed Evolution of Enzymes for Bioorthogonal Chemistry Using Acid Chloride Proximity Labeling.

Ashley N Ogorek, Shubhashree Pani, Eli J Mertick-Sykes, Jelena Momirov, Yichong Lao, Fernando Banales Mejia, Rachel S T Chan, Xuhui Huang, Bryan C Dickinson, Jeffrey D Martell

Abstract read
In one paragraph

Article in ACS central science, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Evolving faster proximity chemistry.Nature chemical biology · 2026
    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

10 authors.

Ashley N OgorekDepartment of Chemistry, University of Wisconsin-Madison, Madison, Wisconsin 53706, United States.
Shubhashree PaniDepartment of Chemistry,University of Chicago, 5735 S. Ellis Ave., Chicago, Illinois 60637, United States.
Eli J Mertick-SykesDepartment of Chemistry, University of Wisconsin-Madison, Madison, Wisconsin 53706, United States.
Jelena MomirovDepartment of Chemistry,University of Chicago, 5735 S. Ellis Ave., Chicago, Illinois 60637, United States.
Yichong LaoDepartment of Chemistry, University of Wisconsin-Madison, Madison, Wisconsin 53706, United States.
Fernando Banales MejiaDepartment of Chemistry,University of Chicago, 5735 S. Ellis Ave., Chicago, Illinois 60637, United States.
Rachel S T ChanDepartment of Chemistry,University of Chicago, 5735 S. Ellis Ave., Chicago, Illinois 60637, United States.
Xuhui HuangDepartment of Chemistry, University of Wisconsin-Madison, Madison, Wisconsin 53706, United States.ORCID https://orcid.org/0000-0002-7119-9358
Bryan C DickinsonDepartment of Chemistry,University of Chicago, 5735 S. Ellis Ave., Chicago, Illinois 60637, United States.ORCID https://orcid.org/0000-0002-9616-1911
Jeffrey D MartellDepartment of Chemistry, University of Wisconsin-Madison, Madison, Wisconsin 53706, United States.ORCID https://orcid.org/0000-0003-2084-6401

Funding

Hybrid Biological-Abiotic Proximity Labeling Catalysts for Enhancing Spatially-Resolved ProteomicsR01GM150698 · NIGMS · UNIVERSITY OF WISCONSIN-MADISON · PI Jeffrey Daniel Martell · 2023 to 2026
$1.5M
NIGMS NIH HHS R01 GM150698
6 · The paper itself

Abstract

Combining bioorthogonal protecting groups with localized catalysts that can unmask them is a powerful approach to spatially and temporally modulate molecular activity. Enzymes are appealing catalysts in this context because they are genetically targetable, but enzymes are not always available to unmask a protecting group of interest. Here, we report a platform for ultrahigh-throughput enzyme evolution by combining yeast surface display with masked acylating probes, which selectively label yeast cells based on target biocatalytic activity. We introduce the phenylcyclopropyl (pCP) ester protecting group, which has improved bioorthogonality compared to existing ester protecting groups, and use our platform to evolve BS2 esterase for enhanced pCP unmasking. Evolved BS2 mutants are up to 232-fold more active toward the pCP group. Taking advantage of the enhanced bioorthogonality of the pCP group, we applied a pCP probe together with evolved BS2 to perform spatially resolved RNA tagging with high spatial specificity, including in mammalian cell lines with high endogenous esterase activity. Overall, this work delivers a new bioorthogonal protecting group and engineered enzymes capable of unmasking it, and more broadly, it provides a platform to rapidly engineer enzymes for protecting group removal, opening opportunities in imaging, proximity tagging, induced cell signaling, and therapeutics.

Identifiers

PMID41768769
PMCPMC12947558

What OpenQuestion holds

Textmetadata
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.