Evidence map›Paper›PMID 40659637›Full record

ArticleNature communications2025

Regulating the N-oxidation selectivity of P450BM3 monooxygenases for N-heterocycles through computer-assisted structure-guided design.

Liu Yang, Zhongji Pu, Jianping Wu, Xiaofeng Liu, Zhe Wang, Haoran Yu, Liuwei Wang, Yan Meng, Gang Xu, Lirong Yang and 1 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Article
  2. 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

11 authors.

Liu Yang *Institute of Bioengineering, College of Chemical and Biological Engineering, Zhejiang University, Hangzhou, 310058, China.
Zhongji Pu *Xianghu laboratory, Hangzhou, 311231, China.
Jianping WuInstitute of Bioengineering, College of Chemical and Biological Engineering, Zhejiang University, Hangzhou, 310058, China.ORCID http://orcid.org/0000-0002-9924-7307
Xiaofeng LiuShaoxing Institute, Zhejiang University, Shaoxing, 312000, China.
Zhe WangInstitute of Bioengineering, College of Chemical and Biological Engineering, Zhejiang University, Hangzhou, 310058, China.
Haoran YuInstitute of Bioengineering, College of Chemical and Biological Engineering, Zhejiang University, Hangzhou, 310058, China.ORCID http://orcid.org/0000-0001-9012-4688
Liuwei WangInstitute of Bioengineering, College of Chemical and Biological Engineering, Zhejiang University, Hangzhou, 310058, China.
Yan MengInstitute of Bioengineering, College of Chemical and Biological Engineering, Zhejiang University, Hangzhou, 310058, China.
Gang XuInstitute of Bioengineering, College of Chemical and Biological Engineering, Zhejiang University, Hangzhou, 310058, China.
Lirong YangInstitute of Bioengineering, College of Chemical and Biological Engineering, Zhejiang University, Hangzhou, 310058, China.ORCID http://orcid.org/0000-0002-6378-8451
Wenlong ZhengInstitute of Bioengineering, College of Chemical and Biological Engineering, Zhejiang University, Hangzhou, 310058, China. per@zju.edu.cn.ORCID http://orcid.org/0000-0002-9700-7721

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

N-oxidation of N-heterocycles is essential in the synthesis of natural products but challenging due to low efficacy and poor regioselectivity. In this study, the N-oxidation selective potential of P450BM3 from Bacillus megaterium for N-heterocyclic compounds is investigated. Here, twelve amino acids located in the active center, including A74, L75, V78, A82, F87, I263, A264, A328, P329, A330, I401, and L437, are investigated by site-saturation mutation. As a result, F87, A264, L75, V78, A328, I401, and L437 are identified as hotspot residues. Subsequently, the combinatorial active-site saturation test/iterative saturation mutagenesis strategy is performed. Using quinoline as a model substrate, the mutant F87G/A264G/A328L exhibits N-oxidation selectivity of up to 99.0%, with a conversion rate of 99.3%. Molecular dynamics simulations uncover a "push-pull" molecular mechanism elucidating the pivotal role of steric factors in determining substrate recognition and N-oxidation selectivity. This study provides an efficient N-oxide synthesis method and insights into P450BM3's molecular mechanisms.

Indexed as

Bacillus megateriumBacterial ProteinsCytochrome P-450 Enzyme SystemHeterocyclic CompoundsNADPH-Ferrihemoprotein ReductaseCatalytic DomainMolecular Dynamics SimulationMutagenesis, Site-DirectedMutationOxidation-ReductionQuinolinesSubstrate SpecificityBacterial ProteinsCytochrome P-450 Enzyme Systemflavocytochrome P450 BM3 monoxygenasesHeterocyclic CompoundsNADPH-Ferrihemoprotein ReductaseQuinolines

Identifiers

PMID40659637
PMCPMC12259962

What OpenQuestion holds

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LicenceCC BY-NC-ND
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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.