Evidence map›Paper›PMID 41755816›Full record

ArticleJACS Au2026

Clock-Turning Control of P450 TxtE Regioselectivity Enables Precise Site Functionalization of Aromatic Compounds.

Xin Yang, Yue Pan, Tingwei Miao, Zhaoting Yuan, Yalong Cong, Bohuan Fang, Xin Yan, Jiameng Zhang, Ruyi Chen, Yinghui Feng and 3 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in JACS Au, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

13 authors.

Xin YangShanghai Engineering Research Center of Molecular Therapeutics & New Drug Development, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai 200062, China.
Yue PanShanghai Engineering Research Center of Molecular Therapeutics & New Drug Development, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai 200062, China.
Tingwei MiaoShanghai Engineering Research Center of Molecular Therapeutics & New Drug Development, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai 200062, China.
Zhaoting YuanShanghai Engineering Research Center of Molecular Therapeutics & New Drug Development, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai 200062, China.ORCID https://orcid.org/0000-0001-6771-7426
Yalong CongShanghai Engineering Research Center of Molecular Therapeutics & New Drug Development, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai 200062, China.ORCID https://orcid.org/0000-0002-0910-811X
Bohuan FangDepartment of Micro/Nano Electronics, School of Electronic Information and Electrical Engineering, Shanghai Jiaotong University, Shanghai 200240, China.
Xin YanShanghai Engineering Research Center of Molecular Therapeutics & New Drug Development, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai 200062, China.
Jiameng ZhangShanghai Engineering Research Center of Molecular Therapeutics & New Drug Development, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai 200062, China.
Ruyi ChenSchool of Biotechnology, East China University of Science and Technology, Shanghai 200237, China.
Yinghui FengShanghai Engineering Research Center of Molecular Therapeutics & New Drug Development, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai 200062, China.
Zenghui ZhangShanghai Engineering Research Center of Molecular Therapeutics & New Drug Development, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai 200062, China.
Bei GaoSchool of Biotechnology, East China University of Science and Technology, Shanghai 200237, China.ORCID https://orcid.org/0000-0002-1506-6198
Lujia ZhangShanghai Engineering Research Center of Molecular Therapeutics & New Drug Development, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai 200062, China.ORCID https://orcid.org/0000-0003-3566-917X

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Aromatic nitration is a key transformation in the synthesis of pharmaceuticals, functional materials, and fine chemicals, yet selective functionalization of electronically deactivated sites remains a formidable challenge. The C6 position of l-tryptophan is particularly inert due to the high conjugation and low electron density of the indole ring, and no chemical or enzymatic system has achieved efficient single-step nitration at this site. Here we report a computer-aided regioselective design platform that precisely reprograms cytochrome P450 TxtE to enable C6-selective nitration. Guided by MD simulations, MM/PBSA energy decomposition, and QM/MM calculations, we identified key residues that control substrate orientation and engineered the H176F/A248F double mutant, which achieves >99% C6 selectivity with the highest total turnover number among all variants. High-resolution crystallographic analysis (1.53 Å) combined with QM/MM calculations revealed that, in the H176FA248F, steric repacking of the active pocket and substrate flipping lower the C6 nitration barrier from 54.3 kcal·mol

Indexed as

C6-functionalizationclock turningcomputer-aided enzyme designcytochrome P450 TxtErational designregioselective nitration

Identifiers

PMID41755816
PMCPMC12933299

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Registered trials

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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.