Evidence map›Paper›PMID 36575800›Full record

ArticlePlant communications2023

MEP pathway products allosterically promote monomerization of deoxy-D-xylulose-5-phosphate synthase to feedback-regulate their supply.

Xueni Di, David Ortega-Alarcon, Ramu Kakumanu, Javier Iglesias-Fernandez, Lucia Diaz, Edward E K Baidoo, Adrian Velazquez-Campoy, Manuel Rodríguez-Concepción, Jordi Perez-Gil

Open access · goldAbstract read
In one paragraph

Article in Plant communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed
3.1field-weighted citation impact, top 7% 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

25 citing papers in PubMed, 42 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

9 authors at 3 institutions in 2 countries.

Xueni DiInstitute for Plant Molecular and Cell Biology (IBMCP), CSIC-Universitat Politècnica de València, 46022 Valencia, Spain; Centre for Research in Agricultural Genomics (CRAG), CSIC-IRTA-UAB-UB, Campus UAB Bellaterra, 08193 Barcelona, Spain.
David Ortega-AlarconInstitute for Biocomputation and Physics of Complex Systems (BIFI), Joint Unit GBsC-CSIC-BIFI, Universidad de Zaragoza, 50009 Zaragoza, Spain; Departamento de Bioquímica y Biología Molecular y Celular, Universidad de Zaragoza, 50009 Zaragoza, Spain.
Ramu KakumanuJoint BioEnergy Institute, 5885 Hollis Street, Emeryville, CA 94608, USA; Biological Systems and Engineering Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA.
Javier Iglesias-FernandezNostrum Biodiscovery SL, 08029 Barcelona, Spain.
Lucia DiazNostrum Biodiscovery SL, 08029 Barcelona, Spain.
Edward E K BaidooJoint BioEnergy Institute, 5885 Hollis Street, Emeryville, CA 94608, USA; Biological Systems and Engineering Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA.
Adrian Velazquez-CampoyInstitute for Biocomputation and Physics of Complex Systems (BIFI), Joint Unit GBsC-CSIC-BIFI, Universidad de Zaragoza, 50009 Zaragoza, Spain; Departamento de Bioquímica y Biología Molecular y Celular, Universidad de Zaragoza, 50009 Zaragoza, Spain; Instituto de Investigación Sanitaria de Aragón (IIS Aragon), 50009 Zaragoza, Spain; Centro de Investigación Biomédica en Red en el Área Temática de Enfermedades Hepáticas y Digestivas (CIBERehd), 28029 Madrid, Spain.
Manuel Rodríguez-ConcepciónInstitute for Plant Molecular and Cell Biology (IBMCP), CSIC-Universitat Politècnica de València, 46022 Valencia, Spain; Centre for Research in Agricultural Genomics (CRAG), CSIC-IRTA-UAB-UB, Campus UAB Bellaterra, 08193 Barcelona, Spain. Electronic address: manuelrc@ibmcp.upv.es.
Jordi Perez-GilCentre for Research in Agricultural Genomics (CRAG), CSIC-IRTA-UAB-UB, Campus UAB Bellaterra, 08193 Barcelona, Spain. Electronic address: jordi.perez@cragenomica.es.
Center for Research in Agricultural Genomics · ESLawrence Berkeley National Laboratory · USUniversidad de Zaragoza · ES

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Isoprenoids are a very large and diverse family of metabolites required by all living organisms. All isoprenoids derive from the double-bond isomers isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP), which are produced by the methylerythritol 4-phosphate (MEP) pathway in bacteria and plant plastids. It has been reported that IPP and DMAPP feedback-regulate the activity of deoxyxylulose 5-phosphate synthase (DXS), a dimeric enzyme that catalyzes the main flux-controlling step of the MEP pathway. Here we provide experimental insights into the underlying mechanism. Isothermal titration calorimetry and dynamic light scattering approaches showed that IPP and DMAPP can allosterically bind to DXS in vitro, causing a size shift. In silico ligand binding site analysis and docking calculations identified a potential allosteric site in the contact region between the two monomers of the active DXS dimer. Modulation of IPP and DMAPP contents in vivo followed by immunoblot analyses confirmed that high IPP/DMAPP levels resulted in monomerization and eventual aggregation of the enzyme in bacterial and plant cells. Loss of the enzymatically active dimeric conformation allows a fast and reversible reduction of DXS activity in response to a sudden increase or decrease in IPP/DMAPP supply, whereas aggregation and subsequent removal of monomers that would otherwise be available for dimerization appears to be a more drastic response in the case of persistent IPP/DMAPP overabundance (e.g., by a blockage in their conversion to downstream isoprenoids). Our results represent an important step toward understanding the regulation of the MEP pathway and rational design of biotechnological endeavors aimed at increasing isoprenoid contents in microbial and plant systems.

Indexed as

PlantsTerpenesErythritolFeedbackHemiterpenesOrganophosphorus CompoundsPentosephosphatesPhosphatesSugar Phosphates2-C-methylerythritol 4-phosphate3,3-dimethylallyl pyrophosphateErythritolHemiterpenesOrganophosphorus CompoundsPentosephosphatesPhosphatesSugar PhosphatesTerpenesxylulose-5-phosphateallostericDXSfeedback regulationisoprenoidsmonomerization

Identifiers

PMID36575800
PMCPMC10203381
OpenAlexW4312220333

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.