Evidence map›Paper›PMID 40556721›Full record

ArticleChemical science2025

Biosynthesis of reveromycin derivatives by altering the regioselectivity of cytochrome P450revI.

Ya Fen Yong, Song Liu, Katsuyuki Sakai, Keisuke Fujiyama, Hiroshi Takagi, Yushi Futamura, Takeshi Shimizu, Hiroyuki Osada, Eugene Boon Beng Ong, Shunji Takahashi

Abstract read
In one paragraph

Article in Chemical science, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0cells of the map it votes in
0citing papers in PubMed
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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

10 authors.

Ya Fen YongNatural Product Biosynthesis Research Unit, RIKEN Center for Sustainable Resource Science Wako Saitama 351-0198 Japan shunjitaka@riken.jp.ORCID https://orcid.org/0000-0002-8979-1771
Song LiuNatural Product Biosynthesis Research Unit, RIKEN Center for Sustainable Resource Science Wako Saitama 351-0198 Japan shunjitaka@riken.jp.
Katsuyuki SakaiNatural Product Biosynthesis Research Unit, RIKEN Center for Sustainable Resource Science Wako Saitama 351-0198 Japan shunjitaka@riken.jp.ORCID https://orcid.org/0000-0001-9210-6176
Keisuke FujiyamaNatural Product Biosynthesis Research Unit, RIKEN Center for Sustainable Resource Science Wako Saitama 351-0198 Japan shunjitaka@riken.jp.ORCID https://orcid.org/0000-0003-0960-353X
Hiroshi TakagiNatural Product Biosynthesis Research Unit, RIKEN Center for Sustainable Resource Science Wako Saitama 351-0198 Japan shunjitaka@riken.jp.
Yushi FutamuraChemical Resource Development Research Unit and Drug Discovery Chemical Bank Unit, RIKEN Center for Sustainable Resource Science Wako Saitama 351-0198 Japan.ORCID https://orcid.org/0000-0002-4224-6944
Takeshi ShimizuChemical Resource Development Research Unit and Drug Discovery Chemical Bank Unit, RIKEN Center for Sustainable Resource Science Wako Saitama 351-0198 Japan.
Hiroyuki OsadaChemical Resource Development Research Unit and Drug Discovery Chemical Bank Unit, RIKEN Center for Sustainable Resource Science Wako Saitama 351-0198 Japan.ORCID https://orcid.org/0000-0002-3606-4925
Eugene Boon Beng OngInstitute for Research in Molecular Medicine, Universiti Sains Malaysia 11800 USM Penang Malaysia.ORCID https://orcid.org/0000-0001-6259-9029
Shunji TakahashiNatural Product Biosynthesis Research Unit, RIKEN Center for Sustainable Resource Science Wako Saitama 351-0198 Japan shunjitaka@riken.jp.ORCID https://orcid.org/0000-0003-1684-9298

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Reveromycin A (RM-A) (1) has a 6,6-spiroacetal core structure that is important for its biological activity. However, 1 undergoes a spiroacetal rearrangement to form RM-B (2) with a 5,6-spiroacetal core, which exhibits reduced bioactivity. This undesired rearrangement is partly due to the hemisuccinate moiety at the C18 position of 1. In 1 biosynthesis, P450revI catalyses the C18-hydroxylation of RM-T (3), which is essential for its subsequent hemisuccinylation to generate 1. In this study, we aimed to alter the P450revI regioselectivity to improve the stability of the 6,6-spiroacetal core and expand the structural diversity of RMs. Candidate amino acid residues for mutagenesis studies were selected by comparing the co-crystal structure of P450revI with the docking models of the P450revI mutant-3 complexes. Notably, the P450revI-A241L mutant selectively produced novel RM derivatives. Nuclear magnetic resonance analysis revealed that P450revI-A241L catalysed the C17-hydroxylation of 3 to produce 17-hydroxy-RM-T (6). Co-crystal structure analysis of the P450revI-A241L-3 complex revealed that the pro-

Identifiers

PMID40556721
PMCPMC12183568

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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.