The study reveals how cells can be pushed into producing more internal energy leading to better cell factories.

Researchers have uncovered some of the secrets of how cells generate and use energy. A new study has revealed it is possible to evoke a shift in the metabolism from fermentation to respiration of E. coli and baker’s yeast by toying with fermentation conditions.

More ATPs

What this means is that the cells can be pushed into producing more internal energy leading to better cell factories. “This information can be used to design new, improved cell factories,” said corresponding author Professor at Chalmers University of Technology, Sweden, and Scientific Director at The Novo Nordisk Foundation Center for Biosustainability at DTU in Denmark Jens Nielsen.

Cells use sugar glucose to constantly produce high-energy molecules called ATP. ATPs serve as the cellular “food” consumed by the enzymes within cells in order to build biomass or do other cellular work.

As such, the more ATP can be generated, the better the enzymes can perform. The researchers discovered that ATP can be generated by either of two pathways.

The first is a high-yielding respiratory pathway resulting in 23.5 ATPs per glucose molecule. The second is a low-yielding fermentative pathway of only 11 ATPs per glucose molecule.

The researchers found further evidence that the two pathways supplement each other. However, they were able to shift the natural balance between the two by changing the conditions of the fermentation and the amount of sugar and protein available. 

The researchers further revealed that making some key enzymes perform better meant that the cells changed from doing low yielding fermentative metabolism to breathing through the high yielding respiratory metabolism.

Bypassing the build-up of fermentative byproducts

This shift was found to both produce more intracellular ATP while bypassing the build-up of fermentative byproducts; acetate in E. coli and ethanol in baker’s yeast. “These byproducts are unwanted and decrease the yield of the sought-for molecules you want to produce in your cell factory,” said Nielsen.

Ultimately what the researchers uncovered was that the cells performing their best actually used both pathways. In addition, they revealed that the more proteins were available the more efficient was a pathway.

In conclusion, in order to get better performing cells in fermentations, it is best to allocate more protein to the high-yielding pathway.

The research has been published in Proceedings of the National Academy of Sciences (PNAS).