Functional Metabolomics Describes the Yeast Biosynthetic Regulome.
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.
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.
Michael
M
Mülleder
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.
Enrica
E
Calvani
Department of Biochemistry and Cambridge Systems Biology Centre, University of Cambridge, Cambridge CB2 1GA, UK.
Mohammad Tauqeer
MT
Alam
Department of Biochemistry and Cambridge Systems Biology Centre, University of Cambridge, Cambridge CB2 1GA, UK.
Richard Kangda
RK
Wang
Department of Biochemistry and Cambridge Systems Biology Centre, University of Cambridge, Cambridge CB2 1GA, UK.
Florian
F
Eckerstorfer
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.
Aleksej
A
Zelezniak
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.
Markus
M
Ralser
D000596:Amino Acids / Q000096:biosynthesis* / Q000235:genetics; D002843:Chromatin / Q000378:metabolism; D017353:Gene Deletion; D015966:Gene Expression Regulation, Fungal; D053263:Gene Regulatory Networks; D055442:Metabolome / Q000235:genetics; D055432:Metabolomics / Q000379:methods; D005810:Multigene Family; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic
D000596:Amino Acids; D002843:Chromatin; D019869:Phosphatidylinositol 3-Kinases; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; C561842:TORC1 protein complex, S cerevisiae; C083324:TOR1 protein, S cerevisiae
amino acids; functional gene annotation; functional metabolomics; mass spectrometry; metabolism; target of rapamycin (TOR); unknown gene function; vesicle mediated transport; yeast gene deletion collection
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