Mülleder, Michael, Calvani, Enrica, Alam, Mohammad T., Wang, Richard Kangda, Eckerstorfer, Florian, Zelezniak, Aleksej and Ralser, Markus (2016) Functional metabolomics describes the yeast biosynthetic regulome. Cell, 167 (2). 553-565.e12.

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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.

Item Type:	Journal Article
Subjects:	Q Science > QH Natural history Q Science > QK Botany Q Science > QP Physiology
Divisions:	Faculty of Medicine > Warwick Medical School > Biomedical Sciences > Cell & Developmental Biology Faculty of Medicine > Warwick Medical School > Biomedical Sciences Faculty of Medicine > Warwick Medical School
Library of Congress Subject Headings (LCSH):	Yeast -- Genetic aspects, Saccharomyces -- Genetic aspects, Metabolites
Journal or Publication Title:	Cell
Publisher:	Cell Press
ISSN:	1097-4172
Official Date:	6 October 2016
Dates:	Date Event 6 October 2016 Published 29 September 2016 Available 2 September 2016 Accepted 23 October 2015 Submitted
Date of first compliant deposit:	8 March 2017
Volume:	167
Number:	2
Page Range:	553-565.e12
Status:	Peer Reviewed
Publication Status:	Published
Access rights to Published version:	Open Access
Funder:	Francis Crick Institute, Cancer Research UK (CRUK), Medical Research Council (Great Britain) (MRC), Wellcome Trust (London, England), European Research Council (ERC), European Commission (EC), Marie Skłodowska-Curie actions
Grant number:	FC001134 (CRUK), FC001134 (MRC), FC001134, RG093735/Z/10/Z, 200829/Z/16/Z (Wellcome Trust), Grant 260809 (ERC), ALTF-969 2014 (EC), LTFCOFUND2013 GA-2013-609409 (Marie Skłodowska-Curie actions)

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