Evidence map›Paper›PMID 42869905›Full record

ArticleNature communications2026

Reprogramming the Rossmann fold signature motif creates orthogonal redox biocatalysts.

Yu Ping, Jin Young Kim, Minh-Anh L Dinh, Emma Luu, Suphanida Worakaensai, Shiding Zhang, William B Black, Emma Monge, Hans Jefferson C Ng, Sean Perea and 5 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 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. 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

15 authors.

Yu Ping *Department of Chemical and Biomolecular Engineering, University of California, Irvine, Irvine, CA, USA.
Jin Young Kim *Department of Chemical and Biomolecular Engineering, University of California, Irvine, Irvine, CA, USA.
Minh-Anh L Dinh *Department of Chemical and Biomolecular Engineering, University of California, Irvine, Irvine, CA, USA.ORCID 0009-0003-3914-2882
Emma Luu *Genome Center, University of California, Davis, Davis, CA, USA.ORCID 0000-0002-0388-9330
Suphanida WorakaensaiDepartment of Chemical and Biomolecular Engineering, University of California, Irvine, Irvine, CA, USA.
Shiding ZhangDepartment of Chemical and Biomolecular Engineering, University of California, Irvine, Irvine, CA, USA.ORCID 0009-0003-3497-820X
William B BlackDepartment of Chemical and Biomolecular Engineering, University of California, Irvine, Irvine, CA, USA.ORCID 0009-0007-2851-9997
Emma MongeDepartment of Biological Chemistry, University of California, Irvine, Irvine, CA, USA.
Hans Jefferson C NgDepartment of Chemical and Biomolecular Engineering, University of California, Irvine, Irvine, CA, USA.
Sean PereaDepartment of Chemical and Biomolecular Engineering, University of California, Irvine, Irvine, CA, USA.
Yulai ZhangDepartment of Chemical and Biomolecular Engineering, University of California, Irvine, Irvine, CA, USA.
Youtian CuiGenome Center, University of California, Davis, Davis, CA, USA.
Edward KingDepartment of Molecular Biology and Biochemistry, University of California, Irvine, Irvine, CA, USA.
Justin B SiegelGenome Center, University of California, Davis, Davis, CA, USA.
Han LiDepartment of Chemical and Biomolecular Engineering, University of California, Irvine, Irvine, CA, USA. han.li@uci.edu.ORCID 0000-0002-6113-6433

Funding

Workshop on Environmental Technology Transfer and EntrepreneurshipP42ES004699 · NIEHS · UNIVERSITY OF CALIFORNIA DAVIS · PI HAMMOCK, BRUCE D · 1987 to 2021
$50.1M
Enzymatic formation of the hydrocarbon skeletons underlying diterpenoid diversityR01GM076324 · NIGMS · IOWA STATE UNIVERSITY · PI PETERS, REUBEN JOHN · 2006 to 2019
$3.4M
Expanding the Metabolic Currencies of LifeR35GM153401 · NIGMS · UNIVERSITY OF CALIFORNIA-IRVINE · PI Han Li · 2024 to 2026
$1.4M
National Science Foundation (NSF) 1627539National Science Foundation (NSF) 1805510National Science Foundation (NSF) 1827246National Science Foundation (NSF) 2328145National Science Foundation (NSF) 2452698NIEHS NIH HHS P42 ES004699NIGMS NIH HHS R01 GM076324NIGMS NIH HHS R35 GM153401U.S. Department of Health & Human Services | NIH | National Institute of Environmental Health Sciences (NIEHS) P42ES004699U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS) 1R35GM153401U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS) R01 GM 076324-11
6 · The paper itself

Abstract

Biological reducing power is carried by nicotinamide adenine dinucleotide (phosphate) (NAD(P)/H), which supports cellular functions and cannot be specifically directed to engineered metabolic pathways. Nicotinamide mononucleotide (NMN(H)) has emerged as an orthogonal redox cofactor to address this. Herein, to create NMN(H)-specific enzymes that no longer interact with cellular NAD(P)/H pools, we perturb the ancient, conserved GxGxxG motif in Rossmann fold enzymes that enables persistent NAD(P)/H recognition. We build variants NRC-01 and NRC-02 on phosphite dehydrogenase (PTDH), which eliminate electron leaking to NAD(P)H-dependent side reactions while driving NMNH-dependent biotransformation with ~240-fold higher productivity than existing catalysts. Testing the design principle on 12 other vastly diverse enzymes yields additional NMN(H)-orthogonal enzymes catalyzing valuable biomanufacturing reactions, and reveals a potential rule predicting the translatability of this method. Rosetta modeling, structural alignment, and experimental results reveal that Rossmann fold reprogramming, paired with engineered structural reinforcement, may offer a general route to orthogonal redox biocatalysts.

Indexed as

NADH, NADPH OxidoreductasesAmino Acid MotifsBiocatalysisModels, MolecularNADPOxidation-ReductionProtein EngineeringProtein FoldingNADH, NADPH OxidoreductasesNADPNAD phosphite oxidoreductase

Identifiers

PMID42869905
PMCPMC13661529

What OpenQuestion holds

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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.