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Engineering Intracellular Organelles to Increase Production of Useful Chemicals by Confining Their Metabolic Pathways
Published: March 30, 2016
Posted: July 20, 2016

Scientists move closer to engineering metabolic pathways within yeast intracellular compartments tailored for desired purposes.

The Science
Engineering microbes to produce valuable bioproducts or biofuels is often complicated, because the product is deleterious to the cell or the chemical conditions in the cytosol are not favorable for the required chemical reactions. To overcome this challenge, researchers at the University of California (UC), Berkeley, have developed a system to facilitate the introduction of enzymes into the yeast peroxisome, isolating the selected metabolic pathway from the cytosolic environment.

The Impact
The development of a versatile intracellular organelle to confine engineered metabolic pathways will facilitate metabolic engineering. This research advances the repurposing of the yeast peroxisome to isolate synthetic metabolic pathways that would be inefficient if expressed dissolved in the cytosol. This system will make it possible to engineer eukaryotic cells to produce high yields of useful chemicals that cannot be achieved in traditional biological systems.

Summary
High-yield production of bioproducts and fuels in microbial systems requires metabolic flux to be directed toward an engineered pathway. However, this redirection of metabolic flux is difficult to achieve because cells tend to divert metabolic flux toward native cellular processes. Engineered metabolic pathways have been confined to organelles such as the mitochondrion or the vacuole to isolate them from the host's metabolism, but the cell needs those organelles for its normal functions and, therefore, they cannot be completely repurposed. On the other hand, yeast can live without peroxisomes, making this an ideal organelle to isolate newly designed metabolic pathways and their products. A research team at UC Berkeley has discovered a protein signal that allows the efficient targeting of engineered proteins into the peroxisome. The researchers also devised a high-throughput method to measure the efficiency of the process and demonstrated the feasibility of the approach by introducing a simple metabolic pathway that produces a colored compound into the yeast peroxisome. The strategy can now be used to sequester useful metabolic pathways into the peroxisome to produce high yields of valuable chemicals and fuels.

Contacts (BER PM)
Pablo Rabinowicz
Biological and Environmental Research
pablo.rabinowicz@science.doe.gov

(PI Contact)
John Dueber
Bioengineering Department
University of California, Berkeley
jdueber@berkeley.edu

Funding
This work was supported by the Office of Biological and Environmental Research within the U.S. Department of Energy’s Office of Science under Early Career Research Program award DE-SC0008084. Authors also acknowledge support from the National Science Foundation and U.S. Department of Defense.

Publications
DeLoache, W. C., Z. N. Russ, and J. E. Dueber. 2016. “Towards Repurposing the Yeast Peroxisome for Compartmentalizing Heterologous Metabolic Pathways,” Nature Communications 7, 11152. DOI: 10.1038/ncomms11152. (Reference link)

Topic Areas:

  • Research Area: Genomic Analysis and Systems Biology
  • Research Area: Microbes and Communities
  • Research Area: Sustainable Biofuels and Bioproducts
  • Research Area: Biosystems Design
  • Cross-Cutting: Early Career

Division: SC-33.2 Biological Systems Science Division, BER

 

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