Evidence map›Paper›PMID 30266997›Full record

ArticleNature communications2018

Insights into a dual function amide oxidase/macrocyclase from lankacidin biosynthesis.

Jonathan Dorival, Fanny Risser, Christophe Jacob, Sabrina Collin, Gerald Dräger, Cédric Paris, Benjamin Chagot, Andreas Kirschning, Arnaud Gruez, Kira J Weissman

Erratum issuedOpen access · goldAbstract 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. An erratum has been issued. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
1.4field-weighted citation impact, top 21% 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

9 citing papers in PubMed, 23 citations in OpenAlex.

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  7. Modular Approaches to Lankacidin Antibiotics.Journal of the American Chemical Society · 2020
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors at 3 institutions in 2 countries.

Jonathan DorivalUMR 7365, Ingénierie Moléculaire et Physiopathologie Articulaire (IMoPA), CNRS-Université de Lorraine, Biopôle de l'Université de Lorraine, Campus Biologie Santé, 9 Avenue de la Forêt de Haye, BP 20199, 54505, Vandœuvre-lès-Nancy Cedex, France.
Fanny RisserUMR 7365, Ingénierie Moléculaire et Physiopathologie Articulaire (IMoPA), CNRS-Université de Lorraine, Biopôle de l'Université de Lorraine, Campus Biologie Santé, 9 Avenue de la Forêt de Haye, BP 20199, 54505, Vandœuvre-lès-Nancy Cedex, France.
Christophe JacobUMR 7365, Ingénierie Moléculaire et Physiopathologie Articulaire (IMoPA), CNRS-Université de Lorraine, Biopôle de l'Université de Lorraine, Campus Biologie Santé, 9 Avenue de la Forêt de Haye, BP 20199, 54505, Vandœuvre-lès-Nancy Cedex, France.
Sabrina CollinUMR 7365, Ingénierie Moléculaire et Physiopathologie Articulaire (IMoPA), CNRS-Université de Lorraine, Biopôle de l'Université de Lorraine, Campus Biologie Santé, 9 Avenue de la Forêt de Haye, BP 20199, 54505, Vandœuvre-lès-Nancy Cedex, France.
Gerald DrägerInstitut für Organische Chemie, Leibniz Universität Hannover, Schneiderberg 1B, Hannover, 30167, Germany.ORCID http://orcid.org/0000-0003-1988-0469
Cédric ParisLaboratoire d'Ingénierie des Biomolécules, Ecole Nationale Supérieure d'Agronomie et des Industries Alimentaires (ENSAIA), Université de Lorraine, 2 Avenue de la Fôret de Haye, BP 172, 54518, Vandœuvre-lès-Nancy Cedex, France.
Benjamin ChagotUMR 7365, Ingénierie Moléculaire et Physiopathologie Articulaire (IMoPA), CNRS-Université de Lorraine, Biopôle de l'Université de Lorraine, Campus Biologie Santé, 9 Avenue de la Forêt de Haye, BP 20199, 54505, Vandœuvre-lès-Nancy Cedex, France.ORCID http://orcid.org/0000-0002-9153-0060
Andreas KirschningInstitut für Organische Chemie, Leibniz Universität Hannover, Schneiderberg 1B, Hannover, 30167, Germany.
Arnaud GruezUMR 7365, Ingénierie Moléculaire et Physiopathologie Articulaire (IMoPA), CNRS-Université de Lorraine, Biopôle de l'Université de Lorraine, Campus Biologie Santé, 9 Avenue de la Forêt de Haye, BP 20199, 54505, Vandœuvre-lès-Nancy Cedex, France. arnaud.gruez@univ-lorraine.fr.
Kira J WeissmanUMR 7365, Ingénierie Moléculaire et Physiopathologie Articulaire (IMoPA), CNRS-Université de Lorraine, Biopôle de l'Université de Lorraine, Campus Biologie Santé, 9 Avenue de la Forêt de Haye, BP 20199, 54505, Vandœuvre-lès-Nancy Cedex, France. kira.weissman@univ-lorraine.fr.ORCID http://orcid.org/0000-0002-3012-2960
Centre National de la Recherche Scientifique · FRLeibniz University Hannover · DELaboratoire d'Ingénierie des Biomolécules

Funding

EPA EP-C-15-004
6 · The paper itself

Abstract

Acquisition of new catalytic activity is a relatively rare evolutionary event. A striking example appears in the pathway to the antibiotic lankacidin, as a monoamine oxidase (MAO) family member, LkcE, catalyzes both an unusual amide oxidation, and a subsequent intramolecular Mannich reaction to form the polyketide macrocycle. We report evidence here for the molecular basis for this dual activity. The reaction sequence involves several essential active site residues and a conformational change likely comprising an interdomain hinge movement. These features, which have not previously been described in the MAO family, both depend on a unique dimerization mode relative to all structurally characterized members. Taken together, these data add weight to the idea that designing new multifunctional enzymes may require changes in both architecture and catalytic machinery. Encouragingly, however, our data also show LkcE to bind alternative substrates, supporting its potential utility as a general cyclization catalyst in synthetic biology.

Indexed as

AmidesAmino Acid SequenceBacterial ProteinsBiocatalysisBiosynthetic PathwaysMacrolidesModels, ChemicalModels, MolecularMolecular StructureOxidoreductases Acting on CH-NH Group DonorsProtein ConformationProtein MultimerizationSequence Homology, Amino AcidStreptomycesSubstrate SpecificityAmidesamine oxidase, mixed functionBacterial ProteinslankacidinsMacrolidesOxidoreductases Acting on CH-NH Group Donors

Identifiers

PMID30266997
PMCPMC6162330
OpenAlexW2892509725

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.