Evidence map›Paper›PMID 28902839›Full record

ArticleNature2017

SAM-dependent enzyme-catalysed pericyclic reactions in natural product biosynthesis.

Masao Ohashi, Fang Liu, Yang Hai, Mengbin Chen, Man-Cheng Tang, Zhongyue Yang, Michio Sato, Kenji Watanabe, K N Houk, Yi Tang

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers.

0numbers the graph read from it
0cells of the map it votes in
73citing papers in PubMed
15.9field-weighted citation impact, top 1% of its field
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

73 citing papers in PubMed, 194 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Review
  6. Article
  7. Review
  8. Article
  9. Review
  10. Article
  11. Article
  12. Article
  13. Article
  14. A Novel ZnMicroorganisms · 2023
    Article
  15. Natural product reports · 2023
    Review
  16. Article
  17. Article
  18. Article
  19. Article
  20. Article

13 more citing papers are in PubMed but not listed here.

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 at 2 institutions in 2 countries.

Masao OhashiDepartment of Chemical and Biomolecular Engineering, University of California, Los Angeles, Los Angeles, California, USA.
Fang LiuDepartment of Chemistry and Biochemistry, University of California, Los Angeles, Los Angeles, California, USA.
Yang HaiDepartment of Chemical and Biomolecular Engineering, University of California, Los Angeles, Los Angeles, California, USA.
Mengbin ChenDepartment of Chemical and Biomolecular Engineering, University of California, Los Angeles, Los Angeles, California, USA.
Man-Cheng TangDepartment of Chemical and Biomolecular Engineering, University of California, Los Angeles, Los Angeles, California, USA.
Zhongyue YangDepartment of Chemistry and Biochemistry, University of California, Los Angeles, Los Angeles, California, USA.
Michio SatoDepartment of Chemical and Biomolecular Engineering, University of California, Los Angeles, Los Angeles, California, USA.
Kenji WatanabeDepartment of Pharmaceutical Sciences, University of Shizuoka, Shizuoka 422-8526, Japan.
K N HoukDepartment of Chemical and Biomolecular Engineering, University of California, Los Angeles, Los Angeles, California, USA.
Yi TangDepartment of Chemical and Biomolecular Engineering, University of California, Los Angeles, Los Angeles, California, USA.
University of California, Los Angeles · USUniversity of Shizuoka · JP

Funding

MIRA: Enzymology and Self-Resistance of Natural Product BiosynthesisR35GM118056 · NIGMS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Yi Tang · 2016 to 2026
$6.1M
Rediscovering Natural Chemical Diversity -1DP1GM106413DP1GM106413 · NIGMS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI TANG, YI · 2012 to 2016
$3.9M
NIGMS NIH HHS DP1 GM106413NIGMS NIH HHS R35 GM118056
6 · The paper itself

Abstract

Pericyclic reactions-which proceed in a concerted fashion through a cyclic transition state-are among the most powerful synthetic transformations used to make multiple regioselective and stereoselective carbon-carbon bonds. They have been widely applied to the synthesis of biologically active complex natural products containing contiguous stereogenic carbon centres. Despite the prominence of pericyclic reactions in total synthesis, only three naturally existing enzymatic examples (the intramolecular Diels-Alder reaction, and the Cope and the Claisen rearrangements) have been characterized. Here we report a versatile S-adenosyl-l-methionine (SAM)-dependent enzyme, LepI, that can catalyse stereoselective dehydration followed by three pericyclic transformations: intramolecular Diels-Alder and hetero-Diels-Alder reactions via a single ambimodal transition state, and a retro-Claisen rearrangement. Together, these transformations lead to the formation of the dihydropyran core of the fungal natural product, leporin. Combined in vitro enzymatic characterization and computational studies provide insight into how LepI regulates these bifurcating biosynthetic reaction pathways by using SAM as the cofactor. These pathways converge to the desired biosynthetic end product via the (SAM-dependent) retro-Claisen rearrangement catalysed by LepI. We expect that more pericyclic biosynthetic enzymatic transformations remain to be discovered in naturally occurring enzyme 'toolboxes'. The new role of the versatile cofactor SAM is likely to be found in other examples of enzyme catalysis.

Indexed as

BiocatalysisBiosynthetic PathwaysAspergillus nidulansBenzopyransBiological ProductsChromatography, High Pressure LiquidCoenzymesCycloaddition ReactionEscherichia coliPyransPyridonesS-AdenosylmethionineBenzopyransBiological ProductsCoenzymesleporin BPyransPyridonesS-Adenosylmethionine

Identifiers

PMID28902839
PMCPMC5679075
OpenAlexW2754727162

What OpenQuestion holds

Textmetadata
LicenceTDM
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.