Evidence map›Paper›PMID 36899003›Full record

ArticleNature communications2023

Decrypting the programming of β-methylation in virginiamycin M biosynthesis.

Sabrina Collin, Russell J Cox, Cédric Paris, Christophe Jacob, Benjamin Chagot, Kira J Weissman, Arnaud Gruez

Open access · goldFull text read
In one paragraph

Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
2.2field-weighted citation impact, top 14% 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

4 citing papers in PubMed, 9 citations in OpenAlex.

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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

7 authors at 3 institutions in 2 countries.

Sabrina CollinUniversité de Lorraine, CNRS, IMoPA, F-54000, Nancy, France.ORCID 0000-0002-8565-8244
Russell J CoxOCI & BMWZ, Leibniz Universität Hannover, Schneiderberg 38, 30167, Hannover, Germany.ORCID 0000-0002-1844-0157
Cédric ParisUniversité de Lorraine, LIBio, F-54000, Nancy, France.ORCID 0000-0001-8673-3130
Christophe JacobUniversité de Lorraine, CNRS, IMoPA, F-54000, Nancy, France.ORCID 0000-0001-8522-2865
Benjamin ChagotUniversité de Lorraine, CNRS, IMoPA, F-54000, Nancy, France. benjamin.chagot@univ-lorraine.fr.ORCID 0000-0002-9153-0060
Kira J WeissmanUniversité de Lorraine, CNRS, IMoPA, F-54000, Nancy, France. kira.weissman@univ-lorraine.fr.ORCID 0000-0002-3012-2960
Arnaud GruezUniversité de Lorraine, CNRS, IMoPA, F-54000, Nancy, France. arnaud.gruez@univ-lorraine.fr.ORCID 0000-0002-5828-5526
Centre National de la Recherche Scientifique · FRLaboratoire d'Ingénierie des BiomoléculesLeibniz University Hannover · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

During biosynthesis by multi-modular trans-AT polyketide synthases, polyketide structural space can be expanded by conversion of initially-formed electrophilic β-ketones into β-alkyl groups. These multi-step transformations are catalysed by 3-hydroxy-3-methylgluratryl synthase cassettes of enzymes. While mechanistic aspects of these reactions have been delineated, little information is available concerning how the cassettes select the specific polyketide intermediate(s) to target. Here we use integrative structural biology to identify the basis for substrate choice in module 5 of the virginiamycin M trans-AT polyketide synthase. Additionally, we show in vitro that module 7, at minimum, is a potential additional site for β-methylation. Indeed, analysis by HPLC-MS coupled with isotopic labelling and pathway inactivation identifies a metabolite bearing a second β-methyl at the expected position. Collectively, our results demonstrate that several control mechanisms acting in concert underpin β-branching programming. Furthermore, variations in this control - whether natural or by design - open up avenues for diversifying polyketide structures towards high-value derivatives.

Indexed as

StreptomycesMalonatesMethylationModels, MolecularProtein BindingProtein Structure, TertiarySubstrate SpecificityVirginiamycinMalonatesmalonic acidVirginiamycin

Identifiers

PMID36899003
PMCPMC10006238
OpenAlexW4323834296

What OpenQuestion holds

Textfull text, public
LicenceCC BY
measurements read222
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.