Scientists have recently learned how to use light to control specific groups of neurons to better understand the operation of the brain, a development that has transformed areas of neuroscience.

Researchers at Princeton University have now applied a similar method to controlling the metabolism, or basic chemical process, of a living cell.  In a series of experiments, they used light to control genetically modified yeast and increase its output of commercially valuable chemicals. The results offer scientists a powerful new tool to probe and understand the inner working of cells.

“This technique allows us to control the metabolism of cells in an unprecedented way,” said co-lead researcher José L. Avalos, an assistant professor of chemical and biological engineering and Princeton’s Andlinger Center for Energy and the Environment. “It opens the door to controlling metabolism with light.”

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.

“It provides a new tool with the ability to do sophisticated experiments to determine how metabolism works and how to engineer it,” Avalos said.

In a March 21 paper in the journal Nature, the researchers reported that they used light to increase yeast’s production of the chemical isobutanol as much as 5times higher than previously reported levels in peer-reviewed studies The researchers used a genetically modified strain of the yeast Saccharomyces cerevisiae in the experiments.

Isobutanol is an alcohol used in products such as lubricants, gasoline and jet fuel replacements, and plastics. With good compatibility with gasoline infrastructure, isobutanol has properties that could make it a direct substitute for gas as a vehicle fuel. However, most attempts to create isobutanol biofuel have run into difficulties involving cost or scaling production to an industrial level. Although natural yeast fermentation produces isobutanol, it does so in miniscule amounts. Instead, yeast make high volumes of ethanol (the alcohol in beer and wine) and carbon dioxide (a gas that makes bread rise).

“Yeast don’t want to make anything but ethanol; all their systems have evolved to do this,” said Evan M. Zhao, a third-year Ph.D. student in Avalos’ lab and lead author on the Nature paper. “This has been an age-old problem.”

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Or read the 21 March paper, published in the journal Nature.