RapamycinFungusV1, Main, Exploration, bibRecord, 000B01

Functional Metabolomics Describes the Yeast Biosynthetic Regulome.

Identifieur interne : 000B01 ( Main/Exploration ); précédent : 000B00; suivant : 000B02

Functional Metabolomics Describes the Yeast Biosynthetic Regulome.

Auteurs : Michael Mülleder [Royaume-Uni] ; Enrica Calvani [Royaume-Uni] ; Mohammad Tauqeer Alam [Royaume-Uni] ; Richard Kangda Wang [Royaume-Uni] ; Florian Eckerstorfer [Royaume-Uni] ; Aleksej Zelezniak [Royaume-Uni] ; Markus Ralser [Royaume-Uni]

Source :

Cell [ 1097-4172 ] ; 2016.

RBID : pubmed:27693354

Descripteurs français

English descriptors

KwdEn :
- Amino Acids (biosynthesis), Amino Acids (genetics), Chromatin (metabolism), Gene Deletion (MeSH), Gene Expression Regulation, Fungal (MeSH), Gene Regulatory Networks (MeSH), Metabolome (genetics), Metabolomics (methods), Multigene Family (MeSH), Phosphatidylinositol 3-Kinases (genetics), Phosphatidylinositol 3-Kinases (metabolism), Saccharomyces cerevisiae (genetics), Saccharomyces cerevisiae (metabolism), Saccharomyces cerevisiae Proteins (genetics), Saccharomyces cerevisiae Proteins (metabolism), Transcription Factors (genetics), Transcription Factors (metabolism), Transcription, Genetic (MeSH).
MESH :
- chemical , biosynthesis : Amino Acids.
- chemical , genetics : Amino Acids, Phosphatidylinositol 3-Kinases, Saccharomyces cerevisiae Proteins, Transcription Factors.
- chemical , metabolism : Chromatin, Phosphatidylinositol 3-Kinases, Saccharomyces cerevisiae Proteins, Transcription Factors.
- genetics : Metabolome, Saccharomyces cerevisiae.
- metabolism : Saccharomyces cerevisiae.
- methods : Metabolomics.
- Gene Deletion, Gene Expression Regulation, Fungal, Gene Regulatory Networks, Multigene Family, Transcription, Genetic.

Abstract

Genome-metabolism interactions enable cell growth. To probe the extent of these interactions and delineate their functional contributions, we quantified the Saccharomyces amino acid metabolome and its response to systematic gene deletion. Over one-third of coding genes, in particular those important for chromatin dynamics, translation, and transport, contribute to biosynthetic metabolism. Specific amino acid signatures characterize genes of similar function. This enabled us to exploit functional metabolomics to connect metabolic regulators to their effectors, as exemplified by TORC1, whose inhibition in exponentially growing cells is shown to match an interruption in endomembrane transport. Providing orthogonal information compared to physical and genetic interaction networks, metabolomic signatures cluster more than half of the so far uncharacterized yeast genes and provide functional annotation for them. A major part of coding genes is therefore participating in gene-metabolism interactions that expose the metabolism regulatory network and enable access to an underexplored space in gene function.

DOI: 10.1016/j.cell.2016.09.007
PubMed: 27693354
PubMed Central: PMC5055083

Affiliations:

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Le document en format XML

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<term>Amino Acids (genetics)</term>
<term>Chromatin (metabolism)</term>
<term>Gene Deletion (MeSH)</term>
<term>Gene Expression Regulation, Fungal (MeSH)</term>
<term>Gene Regulatory Networks (MeSH)</term>
<term>Metabolome (genetics)</term>
<term>Metabolomics (methods)</term>
<term>Multigene Family (MeSH)</term>
<term>Phosphatidylinositol 3-Kinases (genetics)</term>
<term>Phosphatidylinositol 3-Kinases (metabolism)</term>
<term>Saccharomyces cerevisiae (genetics)</term>
<term>Saccharomyces cerevisiae (metabolism)</term>
<term>Saccharomyces cerevisiae Proteins (genetics)</term>
<term>Saccharomyces cerevisiae Proteins (metabolism)</term>
<term>Transcription Factors (genetics)</term>
<term>Transcription Factors (metabolism)</term>
<term>Transcription, Genetic (MeSH)</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr"><term>Acides aminés (biosynthèse)</term>
<term>Acides aminés (génétique)</term>
<term>Chromatine (métabolisme)</term>
<term>Délétion de gène (MeSH)</term>
<term>Facteurs de transcription (génétique)</term>
<term>Facteurs de transcription (métabolisme)</term>
<term>Famille multigénique (MeSH)</term>
<term>Métabolome (génétique)</term>
<term>Métabolomique (méthodes)</term>
<term>Phosphatidylinositol 3-kinases (génétique)</term>
<term>Phosphatidylinositol 3-kinases (métabolisme)</term>
<term>Protéines de Saccharomyces cerevisiae (génétique)</term>
<term>Protéines de Saccharomyces cerevisiae (métabolisme)</term>
<term>Régulation de l'expression des gènes fongiques (MeSH)</term>
<term>Réseaux de régulation génique (MeSH)</term>
<term>Saccharomyces cerevisiae (génétique)</term>
<term>Saccharomyces cerevisiae (métabolisme)</term>
<term>Transcription génétique (MeSH)</term>
</keywords>
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</keywords>
<keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Amino Acids</term>
<term>Phosphatidylinositol 3-Kinases</term>
<term>Saccharomyces cerevisiae Proteins</term>
<term>Transcription Factors</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Chromatin</term>
<term>Phosphatidylinositol 3-Kinases</term>
<term>Saccharomyces cerevisiae Proteins</term>
<term>Transcription Factors</term>
</keywords>
<keywords scheme="MESH" qualifier="biosynthèse" xml:lang="fr"><term>Acides aminés</term>
</keywords>
<keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Metabolome</term>
<term>Saccharomyces cerevisiae</term>
</keywords>
<keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Acides aminés</term>
<term>Facteurs de transcription</term>
<term>Métabolome</term>
<term>Phosphatidylinositol 3-kinases</term>
<term>Protéines de Saccharomyces cerevisiae</term>
<term>Saccharomyces cerevisiae</term>
</keywords>
<keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Saccharomyces cerevisiae</term>
</keywords>
<keywords scheme="MESH" qualifier="methods" xml:lang="en"><term>Metabolomics</term>
</keywords>
<keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Chromatine</term>
<term>Facteurs de transcription</term>
<term>Phosphatidylinositol 3-kinases</term>
<term>Protéines de Saccharomyces cerevisiae</term>
<term>Saccharomyces cerevisiae</term>
</keywords>
<keywords scheme="MESH" qualifier="méthodes" xml:lang="fr"><term>Métabolomique</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Gene Deletion</term>
<term>Gene Expression Regulation, Fungal</term>
<term>Gene Regulatory Networks</term>
<term>Multigene Family</term>
<term>Transcription, Genetic</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr"><term>Délétion de gène</term>
<term>Famille multigénique</term>
<term>Régulation de l'expression des gènes fongiques</term>
<term>Réseaux de régulation génique</term>
<term>Transcription génétique</term>
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<front><div type="abstract" xml:lang="en">Genome-metabolism interactions enable cell growth. To probe the extent of these interactions and delineate their functional contributions, we quantified the Saccharomyces amino acid metabolome and its response to systematic gene deletion. Over one-third of coding genes, in particular those important for chromatin dynamics, translation, and transport, contribute to biosynthetic metabolism. Specific amino acid signatures characterize genes of similar function. This enabled us to exploit functional metabolomics to connect metabolic regulators to their effectors, as exemplified by TORC1, whose inhibition in exponentially growing cells is shown to match an interruption in endomembrane transport. Providing orthogonal information compared to physical and genetic interaction networks, metabolomic signatures cluster more than half of the so far uncharacterized yeast genes and provide functional annotation for them. A major part of coding genes is therefore participating in gene-metabolism interactions that expose the metabolism regulatory network and enable access to an underexplored space in gene function.</div>
</front>
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<DateCompleted><Year>2017</Year>
<Month>01</Month>
<Day>31</Day>
</DateCompleted>
<DateRevised><Year>2019</Year>
<Month>01</Month>
<Day>13</Day>
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<Issue>2</Issue>
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<Month>Oct</Month>
<Day>06</Day>
</PubDate>
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<Title>Cell</Title>
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<ArticleTitle>Functional Metabolomics Describes the Yeast Biosynthetic Regulome.</ArticleTitle>
<Pagination><MedlinePgn>553-565.e12</MedlinePgn>
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<Abstract><AbstractText>Genome-metabolism interactions enable cell growth. To probe the extent of these interactions and delineate their functional contributions, we quantified the Saccharomyces amino acid metabolome and its response to systematic gene deletion. Over one-third of coding genes, in particular those important for chromatin dynamics, translation, and transport, contribute to biosynthetic metabolism. Specific amino acid signatures characterize genes of similar function. This enabled us to exploit functional metabolomics to connect metabolic regulators to their effectors, as exemplified by TORC1, whose inhibition in exponentially growing cells is shown to match an interruption in endomembrane transport. Providing orthogonal information compared to physical and genetic interaction networks, metabolomic signatures cluster more than half of the so far uncharacterized yeast genes and provide functional annotation for them. A major part of coding genes is therefore participating in gene-metabolism interactions that expose the metabolism regulatory network and enable access to an underexplored space in gene function.</AbstractText>
<CopyrightInformation>Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.</CopyrightInformation>
</Abstract>
<AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Mülleder</LastName>
<ForeName>Michael</ForeName>
<Initials>M</Initials>
<AffiliationInfo><Affiliation>Department of Biochemistry and Cambridge Systems Biology Centre, University of Cambridge, Cambridge CB2 1GA, UK; The Francis Crick Institute, Mill Hill Laboratory, Mill Hill, London NW7 1AA, UK.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Calvani</LastName>
<ForeName>Enrica</ForeName>
<Initials>E</Initials>
<AffiliationInfo><Affiliation>Department of Biochemistry and Cambridge Systems Biology Centre, University of Cambridge, Cambridge CB2 1GA, UK; The Francis Crick Institute, Mill Hill Laboratory, Mill Hill, London NW7 1AA, UK.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Alam</LastName>
<ForeName>Mohammad Tauqeer</ForeName>
<Initials>MT</Initials>
<AffiliationInfo><Affiliation>Department of Biochemistry and Cambridge Systems Biology Centre, University of Cambridge, Cambridge CB2 1GA, UK.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Wang</LastName>
<ForeName>Richard Kangda</ForeName>
<Initials>RK</Initials>
<AffiliationInfo><Affiliation>Department of Biochemistry and Cambridge Systems Biology Centre, University of Cambridge, Cambridge CB2 1GA, UK.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Eckerstorfer</LastName>
<ForeName>Florian</ForeName>
<Initials>F</Initials>
<AffiliationInfo><Affiliation>Department of Biochemistry and Cambridge Systems Biology Centre, University of Cambridge, Cambridge CB2 1GA, UK.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Zelezniak</LastName>
<ForeName>Aleksej</ForeName>
<Initials>A</Initials>
<AffiliationInfo><Affiliation>Department of Biochemistry and Cambridge Systems Biology Centre, University of Cambridge, Cambridge CB2 1GA, UK; The Francis Crick Institute, Mill Hill Laboratory, Mill Hill, London NW7 1AA, UK.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Ralser</LastName>
<ForeName>Markus</ForeName>
<Initials>M</Initials>
<AffiliationInfo><Affiliation>Department of Biochemistry and Cambridge Systems Biology Centre, University of Cambridge, Cambridge CB2 1GA, UK; The Francis Crick Institute, Mill Hill Laboratory, Mill Hill, London NW7 1AA, UK. Electronic address: markus.ralser@crick.ac.uk.</Affiliation>
</AffiliationInfo>
</Author>
</AuthorList>
<Language>eng</Language>
<GrantList CompleteYN="Y"><Grant><GrantID>FC001134</GrantID>
<Agency>Cancer Research UK</Agency>
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Functional Metabolomics Describes the Yeast Biosynthetic Regulome.

Functional Metabolomics Describes the Yeast Biosynthetic Regulome.

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