Evidence map›Paper›PMID 30166552›Full record

ArticleNature communications2018

Reprogramming of the antimycin NRPS-PKS assembly lines inspired by gene evolution.

Takayoshi Awakawa, Takuma Fujioka, Lihan Zhang, Shotaro Hoshino, Zhijuan Hu, Junko Hashimoto, Ikuko Kozone, Haruo Ikeda, Kazuo Shin-Ya, Wen Liu and 1 more

Abstract read
In one paragraph

Article in Nature communications, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.

0numbers the graph read from it
0cells of the map it votes in
32citing 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

32 citing papers in PubMed.

  1. Article
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  10. Biosynthesis of Isonitrile- and Alkyne-Containing Natural Products.Annual review of chemical and biomolecular engineering · 2022
    Review
  11. Article
  12. Review
  13. Article
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  15. Review
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  18. Screening and Isolation of a Novel Polyene-ProducingFrontiers in bioengineering and biotechnology · 2021
    Article
  19. Biosynthesis of depsipeptides, or Depsi: The peptides with varied generations.Protein science : a publication of the Protein Society · 2020
    Review
  20. 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.

Takayoshi AwakawaGraduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan. awakawa@mol.f.u-tokyo.ac.jp.
Takuma FujiokaGraduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan.
Lihan ZhangGraduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan.
Shotaro HoshinoGraduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan.
Zhijuan HuGraduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan.
Junko HashimotoJapan Biological Informatics Consortium, 2-4-7 Aomi, Koto-ku, Tokyo, 135-8073, Japan.
Ikuko KozoneJapan Biological Informatics Consortium, 2-4-7 Aomi, Koto-ku, Tokyo, 135-8073, Japan.
Haruo IkedaLaboratory of Microbial Engineering, Kitasato Institute for Life Sciences, Kitasato University, Kanagawa, 252-0373, Japan.
Kazuo Shin-YaCollaborative Research Institute for Innovative Microbiology, The University of Tokyo, Yayoi 1-1-1, Bunkyo-ku, Tokyo, 113-8657, Japan. k-shinya@aist.go.jp.
Wen LiuState Key Laboratory of Bio-Organic & Natural Products Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Lingling Road 345, 200032, Shanghai, China.
Ikuro AbeGraduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan. abei@mol.f.u-tokyo.ac.jp.ORCID http://orcid.org/0000-0002-3640-888X

Funding

Ministry of Education, Culture, Sports, Science, and Technology (MEXT) JP15H01836, JP16H06443, JP16K13084, and JP17H04763
6 · The paper itself

Abstract

Reprogramming of the NRPS/PKS assembly line is an attractive method for the production of new bioactive molecules. However, it is usually hampered by the loss of intimate domain/module interactions required for the precise control of chain transfer and elongation reactions. In this study, we first establish heterologous expression systems of the unique antimycin-type cyclic depsipeptides: JBIR-06 (tri-lactone) and neoantimycin (tetra-lactone), and engineer their biosyntheses by taking advantage of bioinformatic analyses and evolutionary insights. As a result, we successfully accomplish three manipulations: (i) ring contraction of neoantimycin (from tetra-lactone to tri-lactone), (ii) ring expansion of JBIR-06 (from tri-lactone to tetra-lactone), and (iii) alkyl chain diversification of JBIR-06 by the incorporation of various alkylmalonyl-CoA extender units, to generate a set of unnatural derivatives in practical yields. This study presents a useful strategy for engineering NRPS-PKS module enzymes, based on nature's diversification of the domain and module organizations.

Indexed as

Amino Acid SequenceAntimycin ABenzamidesComputational BiologyEvolution, MolecularMacrolidesMolecular Sequence DataMultienzyme ComplexesMultigene FamilyOrganic ChemicalsPeptide SynthasesPolyketide SynthasesSequence Homology, Amino AcidSubstrate SpecificityantimycinAntimycin ABenzamidesJBIR 06MacrolidesMultienzyme Complexesneoantimycinnon-ribosomal peptide synthaseOrganic ChemicalsPeptide SynthasesPolyketide Synthases

Identifiers

PMID30166552
PMCPMC6117356

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.