PXD074337

PXD074337 is an original dataset announced via ProteomeXchange.

Title	Model-driven analysis reveals oxidative stress adaptation enabling efficient energy utilization in a Crabtree-negative Saccharomyces cerevisiae.
Description	The metabolic engineering of Saccharomyces cerevisiae to abolish the Crabtree effect via a pyruvate dehydrogenase bypass has enabled growth in minimal medium with glucose as the sole carbon source, although at a low growth rate. Adaptive laboratory evolution of the engineered strain (sZJD23), followed by reverse engineering, produced a variant (sZJD28) with significantly improved growth. This is mainly due to a mutation in MED2, which encodes a subunit of the mediator complex and, to a lesser extent, a mutation in GPD1, which encodes a glycerol-3-phosphate dehydrogenase. Here, using quantitative proteomics and enzyme-constrained genome-scale modelling, we show that these mutations jointly enable a more efficient strategy for oxidative stress adaptation and energy utilization. Specifically, the MED2 mutation reshapes the oxidative stress response, including peroxisomal detoxification, while the GPD1 mutation suppresses a suboptimal redox-balancing strategy in the primary strain. Collectively, these changes result in improved flux distribution, lower protein costs in energy metabolism, and potentially enhanced ATP availability. Our findings reveal how specific mutations coordinate stress tolerance and metabolic efficiency to restore growth in engineered Crabtree-negative yeast.
HostingRepository	PRIDE
AnnounceDate	2026-02-13
AnnouncementXML	Submission_2026-02-12_23:17:58.618.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Johannes Fuchs
SpeciesList	scientific name: Saccharomyces cerevisiae (Baker's yeast); NCBI TaxID: NEWT:4932;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2026-02-11 02:28:59	ID requested
⏵ 1	2026-02-12 23:17:59	announced

Dataset with its publication pending

submitter keyword: microbiology

Saccharomyces cerevisiae

metabolism

Crabtree

Eduard J Kerkhoven
contact affiliation	Department of Life Sciences, Chalmers University of Technology, SE-412 96 Gothenburg, Sweden
contact email	eduardk@chalmers.se
lab head
Johannes Fuchs
contact affiliation	Gothenburg University
contact email	johannes.fuchs@gu.se
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/02/PXD074337

PRIDE project URI

• PRIDE
  1. PXD074337
     1. Label: PRIDE project
     2. Name: Model-driven analysis reveals oxidative stress adaptation enabling efficient energy utilization in a Crabtree-negative Saccharomyces cerevisiae.