Sunday, 6 May 2018

Using light to turn yeast into biochemical factories

Researchers have used a combination of light and genetic engineering to controlling the metabolism, or basic chemical process, of a living cell. Building on techniques that already have transformed the field of neuroscience, the researchers used light to control genetically-modified yeast and increase its output of commercially valuable chemicals.

Yeast has been used for centuries to make bread, wine and beer. Through fermentation, yeast cells transform sugar into chemicals that make bread rise and turn grape juice into wine. Using their new technique, the Princeton researchers have now used fermentation and genetically-engineered yeast to produce other chemicals including lactic acid, used in food production and bioplastics, and isobutanol, a commodity chemical and an advanced biofuel.

Light played a key role in the experiment because it allowed the researchers to switch on genes that they had added to the yeast cells. These particular genes are sensitive to light, which can trigger or suppress their activity. In one case, turning on and off a blue light caused the special yeast to alternate between producing ethanol, a product of normal fermentation, and isobutanol, a chemical that normally would kill yeast at sufficiently high concentration.

The achievement of producing these chemicals was significant, but the researchers were intrigued by the development of light's broader role in metabolic research.The researchers started by putting a modified gene from a marine bacterium that is controllable by blue light into yeast's DNA. They then used light to turn on a chemical process that activates enzymes that naturally allow yeast to grow and multiply by eating glucose and secreting ethanol. But while those enzymes are active, ones that influence the production of isobutanol can't work. So the team turned to darkness to switch off the ethanol-producing enzymes to make room for the expression of their competitors.

READ MORE: Yeast helps hunt for new medicines

Scientists have developed a new way to predict potentially useful drugs from a pool of undefined chemicals. They were able to more quickly identify leads that could be used to treat a range of diseases, from infections, to cancer to Alzheimer's. The finding will also help better match drugs to a disease to maximize the benefit and reduce side-effects. See: Yeast news

Using light to control yeast's chemical production offers several advantages over techniques involving pure genetic engineering or chemical additives. For one, light is much faster and cheaper than most alternatives. It's also adjustable, meaning that turning it on and off can toggle the function of live cells on the spot at any point in the fermentation process (as opposed to chemicals, which generally can't be turned off once they are added.) Also, unlike chemical manipulators that diffuse throughout a cell, light can be applied to specific genes without affecting other parts of the cell.

Optogenetics, as the use of light to control genes is called, is already used in neuroscience and other fields, but this the first application of the technology to control cellular metabolism for chemical production. Gregory Stephanopoulos, an MIT chemical engineering professor who was not involved with Princeton's research, called it a turning point in the field of metabolic engineering.


Evan M. Zhao, Yanfei Zhang, Justin Mehl, Helen Park, Makoto A. Lalwani, Jared E. Toettcher, José L. Avalos. Optogenetic regulation of engineered cellular metabolism for microbial chemical production. Nature, 2018; DOI: 10.1038/nature26141

Posted by Dr. Tim Sandle

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