Repository logo
 

High-throughput metabolomics for the design and validation of a diauxic shift model.

Published version
Peer-reviewed

Type

Article

Change log

Authors

Brunnsåker, Daniel  ORCID logo  https://orcid.org/0000-0002-5167-0536
Soni, Nikul K 
Savolainen, Otto I 

Abstract

Saccharomyces cerevisiae is a very well studied organism, yet ∼20% of its proteins remain poorly characterized. Moreover, recent studies seem to indicate that the pace of functional discovery is slow. Previous work has implied that the most probable path forward is via not only automation but fully autonomous systems in which active learning is applied to guide high-throughput experimentation. Development of tools and methods for these types of systems is of paramount importance. In this study we use constrained dynamical flux balance analysis (dFBA) to select ten regulatory deletant strains that are likely to have previously unexplored connections to the diauxic shift. We then analyzed these deletant strains using untargeted metabolomics, generating profiles which were then subsequently investigated to better understand the consequences of the gene deletions in the metabolic reconfiguration of the diauxic shift. We show that metabolic profiles can be utilised to not only gaining insight into cellular transformations such as the diauxic shift, but also on regulatory roles and biological consequences of regulatory gene deletion. We also conclude that untargeted metabolomics is a useful tool for guidance in high-throughput model improvement, and is a fast, sensitive and informative approach appropriate for future large-scale functional analyses of genes. Moreover, it is well-suited for automated approaches due to relative simplicity of processing and the potential to make massively high-throughput.

Description

Funder: The Wallenberg AI, Autonomous Systems and Software Program

Keywords

Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Metabolomics

Journal Title

NPJ Syst Biol Appl

Conference Name

Journal ISSN

2056-7189
2056-7189

Volume Title

9

Publisher

Springer Science and Business Media LLC
Sponsorship
Svenska Forskningsrådet Formas (2020-01690)