Metabolomics

Dataset Information

0

Model-guided development of evolutionarily stable yeast chassis for dicarboxylic acids production


ABSTRACT:

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 rarely been put to rigorous experimental test and assessed at multiomics level. Here, we report two Saccharomyces cerevisiae chassis strains for dicarboxylic acid production based on genome-scale metabolic modelling. The chassis strain, harbouring 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 multiomics analysis revealed flux bypass at peroxisomal malate dehydrogenase that was not accounted in the model. Integration of transcriptomics, proteomics and metabolomics data 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.

INSTRUMENT(S): Gas Chromatography MS -

SUBMITTER: Filipa Pereira 

PROVIDER: MTBLS2007 | MetaboLights | 2021-07-19

REPOSITORIES: MetaboLights

Dataset's files

Source:
Action DRS
MTBLS2007 Other
FILES Other
a_MTBLS2007_GC-MS___metabolite_profiling-1.txt Txt
i_Investigation.txt Txt
m_MTBLS2007_GC-MS___metabolite_profiling_v2_maf.tsv Tabular
Items per page:
1 - 5 of 6

Similar Datasets

2021-07-20 | PXD020611 | Pride
2017-09-16 | GSE101430 | GEO
2022-05-28 | GSE204846 | GEO
2023-02-17 | GSE183745 | GEO
2015-07-25 | E-GEOD-71308 | biostudies-arrayexpress
2011-04-12 | GSE21313 | GEO
2015-07-25 | GSE71308 | GEO
2011-04-11 | E-GEOD-21313 | biostudies-arrayexpress
2014-11-19 | E-GEOD-63438 | biostudies-arrayexpress
2016-01-22 | E-MTAB-4349 | biostudies-arrayexpress