PXD020611

PXD020611 is an original dataset announced via ProteomeXchange.

Title	S. cerevisiae engineered chassis for dicarboxylic acid production
Description	Chassis strain suitable for producing multiple compounds is a central concept in synthetic biology. Design of a chassis using computational, first-principle, models is particularly attractive due to the predictability and control it offers, including against phenotype reversal due to adaptive mutations. Yet, the theory of model-based chassis design has not been put to experimental test. Here, we report two Saccharomyces cerevisiae chassis strains for dicarboxylic acid production based on genome-scale metabolic modelling. The chassis strain, harboring gene knockouts in serine biosynthesis and in pentose-phosphate pathway, is geared for higher flux towards three target products - succinate, fumarate and malate - but does not appreciably secrete any. Introducing modular product-specific mutations resulted in improved secretion of the corresponding acid as predicted by the model. Adaptive laboratory evolution of the chassis-derived producer cells further improved production for succinate and fumarate attesting to the evolutionary robustness of the underlying growth-product coupling. In the case of malate, which exhibited decreased production during evolution, the multi-omics analysis revealed flux bypass at peroxisomal malate dehydrogenase not accounted in the model. Transcriptomics, proteomics and metabolomics analysis showed overall concordance with the flux re-routing predicted by the model. Together, our results provide experimental evidence for model-based design of microbial chassis and have implications for computer-aided design of microbial cell factories.
HostingRepository	PRIDE
AnnounceDate	2021-07-20
AnnouncementXML	Submission_2021-07-19_22:08:14.585.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Frank Stein
SpeciesList	scientific name: Saccharomyces cerevisiae (Baker's yeast); NCBI TaxID: 4932;
ModificationList	TMT6plex-126 reporter+balance reagent acylated residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2020-07-28 05:00:13	ID requested
⏵ 1	2021-07-19 22:08:14	announced

Dataset with its publication pending

submitter keyword: Yeast, chassis cell, adaptive laboratory evolution

Kiran R. Patil
contact affiliation	Structural and Computational Biology Unit, European Molecular Biology Laboratory, Heidelberg, Germany; The Medical Research Council Toxicology Unit, University of Cambridge, Cambridge, UK
contact email	patil@mrc-tox.cam.ac.uk
lab head
Frank Stein
contact affiliation	EMBL
contact email	frank.stein@embl.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD020611
     1. Label: PRIDE project
     2. Name: S. cerevisiae engineered chassis for dicarboxylic acid production