Evidence map›Paper›PMID 42493606›Full record

ArticleNature chemical biology2026

Using enantioselective biosensors to evolve asymmetric biocatalysts.

Simon d'Oelsnitz, Wantae Kim, Nicole N Zhao, Haley Hardtke, Svetlana P Ikonomova, Nina Alperovich, Olga Vasilyeva, Michael J James, Eric S Zigon, Michael B Cory and 7 more

Abstract read
PubMed Publisher
In one paragraph

Article in Nature chemical biology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing 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

5 citing papers in PubMed.

  1. Drugging endosomal flux.Nature chemical biology · 2026
    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

17 authors.

Simon d'OelsnitzSynthetic Biology HIVE, Department of Systems Biology, Harvard Medical School, Boston, MA, USA. simonsnitz@gmail.com.ORCID http://orcid.org/0000-0001-7512-9157
Wantae KimMcKetta Department of Chemical Engineering, University of Texas at Austin, Austin, TX, USA.ORCID http://orcid.org/0000-0002-7702-8525
Nicole N ZhaoDepartment of Systems Biology, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0009-0009-9144-3598
Haley HardtkeDepartment of Molecular Biosciences, University of Texas at Austin, Austin, TX, USA.ORCID http://orcid.org/0000-0002-3718-5286
Svetlana P IkonomovaNational Institute of Standards and Technology, Gaithersburg, MD, USA.ORCID http://orcid.org/0000-0002-1770-056X
Nina AlperovichNational Institute of Standards and Technology, Gaithersburg, MD, USA.
Olga VasilyevaNational Institute of Standards and Technology, Gaithersburg, MD, USA.
Michael J JamesDepartment of Microbiology, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0009-0002-2978-2571
Eric S ZigonWyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA, USA.ORCID http://orcid.org/0009-0007-0621-3209
Michael B CorySynthetic Biology HIVE, Department of Systems Biology, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0002-2509-2939
Charlie D JohnsonDepartment of Molecular Biosciences, University of Texas at Austin, Austin, TX, USA.ORCID http://orcid.org/0000-0003-1853-8514
Andrew D EllingtonDepartment of Molecular Biosciences, University of Texas at Austin, Austin, TX, USA.ORCID http://orcid.org/0000-0001-6246-5338
Quincey A JustmanSynthetic Biology HIVE, Department of Systems Biology, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0009-0002-5395-0272
Michael SpringerSynthetic Biology HIVE, Department of Systems Biology, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0002-3970-6380
Y Jessie ZhangDepartment of Molecular Biosciences, University of Texas at Austin, Austin, TX, USA.ORCID http://orcid.org/0000-0002-9360-5388
Pamela A SilverSynthetic Biology HIVE, Department of Systems Biology, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0002-7856-4071
David RossNational Institute of Standards and Technology, Gaithersburg, MD, USA.ORCID http://orcid.org/0000-0002-7790-218X

Funding

United States Department of Commerce | National Institute of Standards and Technology (NIST) 70NANB21H100U.S. Department of Health and Human Services (U.S. Department of Health & Human Services) GM148356
6 · The paper itself

Abstract

Biocatalysts are prized for their enantioselectivity, but slow chromatographic separations required to measure enantiomeric excess bottleneck their development. To overcome this limitation, we evolve enantioselective transcription factors (eTFs) that convert enzyme-catalyzed enantiomer concentrations into programmable gene expression outputs, focusing on imine reductases. Here, using a massively parallel reporter assay, we measure dose-response curves for over 300,000 transcription factor variants in response to an imine precursor and chiral amine products. We quantify the sensitivity, selectivity and dynamic range across variants generated by random, site-saturation and shuffling mutagenesis, isolating variants with exceptional specificity. High-resolution structures of evolved eTFs elucidate how steric effects enforce enantioselectivity, while charge interactions distinguish the imine from the amines. Using two eTFs, we create an ultrahigh-throughput chiral screen to evolve an imine reductase with inverted enantioselectivity. To support generalizability and speed, we design a genetic circuit that enables TF generation within weeks. Our methods enable rapid measurement of asymmetric reactions, supporting innovation in chemical manufacturing.

Identifiers

PMID42493606

What OpenQuestion holds

Textmetadata
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.