Skip to main content
Go to the home page of the European Commission (opens in new window)
English en
CORDIS - EU research results
CORDIS

Increasing metabolic engineering efficiency using a conditionally quiescent fission yeast mutant

Project description

Yeast mutant study to revolutionise metabolic engineering

Metabolic engineering holds great promise for enabling the industrial-scale production of crucial and valuable substances. However, current microbial metabolic engineering platforms primarily direct consumed nutrients toward population growth rather than chemical output, reducing overall efficiency and production. The EU-funded QuiescentFactory project addresses this challenge by studying a promising mutation of fission yeast and developing it into a novel metabolic engineering chassis and platform. This mutant grows at 26 °C but enters quiescence at 36 °C while retaining metabolic activity, allowing for the optimisation of metabolite production and overcoming current limitations.

Objective

The proposed project aims to solve a major challenge in metabolic engineering. In microbial metabolic engineering platforms, consumed nutrients are primarily invested into population growth instead of the production of chemicals of interest. Our team is studying a temperature-sensitive mutant of fission yeast (Schizosaccharomyces pombe), which grows normally at 26°C, but enters quiescence at 36°C, while at the same time maintaining its metabolic activity. Such an engineering platform could represent the holy grail of the metabolic engineering field - a chassis strain that can stop growing but keeps producing metabolites. Application of such pseudo-quiescent strain would be useful to both industrial and academic players. To develop this mutant into a new metabolic engineering chassis, I will first design a molecular cloning toolkit to perform metabolic engineering in S. pombe, which will enable construction and expression of complex biosynthetic pathways. Second, I will characterize the phenotype of the pseudoquiescent S. pombe mutant using a multi-omics approach. I will generate knowledge about mRNA, protein, metabolite and flux dynamics to delineate a genome-scale metabolic model of the chassis under pseudo-quiescence. Then, I will assess the ability of the S. pombe mutant to overproduce 3 different high-value compounds (kavain via phenylalanine, theophylline via purine and artemisinin precursor via mevalonate). Finally, I intend to reproduce the pseudo-quiescent mutant phenotype in other commonly used yeast species (Saccharomyces cerevisiae and Yarrowia lipolytica). In the short term, this research will deliver a new type of a metabolic engineering chassis for the production of complex chemicals to the metabolic engineering community. In the long term, it will contribute to the development of metabolic engineering as a competitive alternative of total synthesis of chemicals, leading to greener and renewable chemical industry.

Fields of science (EuroSciVoc)

Keywords

Programme(s)

Topic(s)

Funding Scheme

HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships

See all projects funded under this funding scheme

Call for proposal

(opens in new window) HORIZON-WIDERA-2022-TALENTS-04

See all projects funded under this call

Coordinator

USTAV ORGANICKE CHEMIE A BIOCHEMIE, AV CR, V.V.I.
Net EU contribution
€ 166 278,72
Address
FLEMINGOVO NAM. 542/2
166 10 PRAHA 6
Czechia
Region
Česko Praha Hlavní město Praha
Activity type
Research Organisations
Links
Total cost
No data

Partners (2)