How do cells generate and use energy? This question may seem simple, but the answer is anything but easy. Moreover, when working with industrial fermentations, it is crucial to know how microbial cell factories consume energy and how proteins are used for it.
Researchers have now shown that it is possible to induce a shift in metabolism from fermentation to respiration of E. coli and baker's yeast by optimizing fermentation conditions. This shift means that the cells can be made to produce more internal energy (ATP).
"This information can be used to design new, improved cell factories," said the author's author at Chalmers University of Technology, Sweden, and scientific director Jens Nielsen of the Novo Nordisk Foundation Center for Biological Sustainability at DTU Denmark
Together with lead author Postdoc Yu Chen from the Department of Biology and Biotechnology in Chalmers, Jens Nielsen has studied the metabolism of E. coli and baker's yeast using mathematical models and biological experiments. The research has now been published in Proceedings of the National Academy of Sciences ( PNAS ).
Cells are constantly producing high-energy molecules called ATP from sugar glucose. ATP is the cellular "food" consumed by the workers ̵
Using a computational approach, the researchers found that ATP can be produced in two ways: a highly effective airway that yields 23.5 ATP per glucose molecule, or a less-productive fermentative pathway that produces only 11 ATPs per molecule of glucose.
The two pathways complement each other, but the researchers were able to shift the natural balance between the two by altering the fermentation conditions and the amount of sugar and protein available. In addition, they showed that the high yield pathway requires more protein mass than the low yield pathway to consume glucose at the same rate.
They also showed that altering cell performance in some key enzymes causes the cells to move from a low-yielding pathway to fermentative metabolism to respiration through highly efficient respiratory metabolism.
This shift leads to more intracellular ATP, but also avoids the formation of fermentative by-products; Acetate in E. coli and ethanol in baker's yeast.
"These by-products are undesirable and reduce the yield of the molecules you want to produce in your cell factory," says Jens Nielsen.
In addition, investigators showed that cells that did their best did actually use both routes, not just those with high yields, and that more available proteins meant more efficiency in a particular pathway.
The solution for better performance of cells in fermentations is therefore not to eliminate the fermentative path, but to allocate more protein to the productive pathway.
The researchers exposed the microbes to only different fermentation conditions and did not perform any genetic engineering to induce these changes. At the same time, their studies provided an indication of how to manipulate the metabolism of cells through genetic engineering to become more effective in future experiments.
Scientists describe a well-defined mitochondrial proteome in baker's yeast
Yu Chen et al., Energy metabolism controls phenotypes through protein efficiency and allocation, National Academy of Sciences (2019). DOI: 10.1073 / pnas.1906569116
Breath! Respiratory microbes generate more energy (2019, 23 August)
retrieved on 23rd August 2019
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