Yeast Cell Factories

Historically yeast has been used in the production of beer, bread, and wine. Advances in engineering technology have enabled scientists to modify yeast metabolism to produce medicines (e.g. insulin and opioids), chemicals (e.g. lactic acid), nutraceuticals (e.g. resveratrol) and biofuels. Current yeast cell factory strains are restricted to proof-of-principle levels because of limited precursor supply, poor product tolerance and lack of versatility. CHASSY will design and build robust, efficient, yeast cell factory or chassis strains for industrial production of high value compounds

Yeast Species

The CHASSY project will work with Saccharomyces cerevisiae, the original cell factory yeast and two other strains that have specific industrial advantages. Kluyveromyces marxianus, a thermotolerant yeast with a very high specific growth rate and Yarrowia lipolytica which can grow on hydrophobic substrates and accumulate intracellular lipids.

Systems Biology

Systems Biology examines all of the networks that exist inside a cell, an organ, or a whole organism. At the single cell level it provides a holistic view of what genes are being transcribed into proteins, how these proteins (enzymes) are driving reactions in the cell and how these reactions impact on each other. More...Biologists, engineers, and computer scientists collaborate closely to gather biological data, develop technology to analyse the data, and build models to understand and use the data. Using a systems biology approach, that models yeast on a whole-cell level, metabolic networks will be reconfigured for production of optimised levels of key biosynthetic precursors necessary for the production of high value compounds. To identify the relevant targets for metabolic engineering, data from genomics, transcriptomics and proteomics experiments will be used to build improved genome scale metabolic models for all 3 yeasts.

GEMs and Genome Engineering

Building a genome scale metabolic model of a yeast strain involves reconstruction of all the metabolic networks in the cell. The first yeast GEM of Saccharomyces cerevisiae was published in 2003. More...Advances in methodology such as integrating quantitative data on mRNA, protein and metabolite levels and applying flux balance analysis are improving the power and predictive qualities of GEMs. Improved GEMs provide the foundation for design of engineering strategies to optimise and reprogramme metabolism using synthetic biology.

Synthetic Biology

For many centuries humans have been selecting desirable traits in one species and transferring them to another species, e.g. cross-breeding in plants. Now that scientists have a greater understanding of genetics they have developed tools to allow the transfer of genetic material and subsequently the traits associated with it, in a much more controlled way – genetic engineering. Synthetic biology is simply taking this process one step further by creating synthetic genetic material that doesn’t exist in nature and adding it to an organism’s genetic make-up. More...Chassis strains that are produced in this project will be optimised for synthesis of the key precursor molecules necessary for production of valuable lipid and aromatic compounds. Genes and alleles that confer enhanced industrial robustness on yeast strains will also be incorporated into chassis yeasts. Prototype production strains for these high-value metabolites will be developed and tested under industrial conditions. Overall the methodologies established in CHASSY will lead to the creation of more chassis strains for future innovative applications.