Anyone even vaguely familiar with beverages like whiskey probably knows that yeast is what does the fermenting. Yeast is also the key to creating ethanol from crops such as corn. At this point, though, the single-celled organism doesn’t work with other types of plants, including some critical to creating what’s called cellulosic ethanol. These species include the prairie dweller known as switch grass and selected types of trees.

MIT’s Greg Stephanopoulos is bullish on the potential of these plants. He says that with a few key advances — some under scrutiny in his own lab — “we could be producing 1,500 to 2,500 gallons of cellulosic ethanol for each acre planted in crops like these.” This is a level that would make the government’s goal of using biofuels to meet 40 percent of the U.S.’s liquid-fuel needs look doable. Moreover, the main rap on today’s ethanol — the high energy and other costs involved in growing the corn to make it — doesn’t apply to these species. “With cellulosic ethanol, the energy balance is very positive,” says Stephanopoulos, a chemical engineering professor.

But ordinary yeast’s ineffectiveness with species like switch grass dictates new approaches to turning the sugars obtained from these plants into ethanol. Stephanopoulos is working on those new directions. The faculty member’s an expert in metabolic engineering, which unlike traditional genetic engineering, takes a systems view of how cells work, and seeks to alter them by changing the activities of many genes at time. His specific goals include new forms of both yeast and a commonplace type of bacteria, E. coli, that can help us boost our ethanol supplies.

The context is a need for engineered versions of yeast and E. coli that can convert all the sugars obtained from cellulosic sources into ethanol. Thanks to work elsewhere, the task is partly done: there are already E. coli variants, Stephanopoulos notes, that can do the work of conversion. Unfortunately, they don’t thrive in the role.

“Remember,” he notes, “we’re trying to make a product, ethanol, which many microorganisms don’t like.”Stephanopoulos has been working to generate yeast and E. coli that get along as well in an ethanol environment as fish in the sea. He also wants to generate mutants whose genetic traits are easy to, in effect, catalog — a prelude for making the needed genetic changes transferable to other types of microorganisms.

How to go about this? To illustrate using E. coli as an example, Stephanopoulos first generates variants with many different mutations in a master gene called the sigma factor — a kind of battlefield commander that’s effectively in charge of numerous other genes. Then, he says, “we introduce those mutants into ethanol, and see which ones survive.”

Stephanopoulos has already created mutant yeast and E. coli that do just fine in ethanol. Although further work is needed, his efforts should help set the stage for large-scale ethanol production — and Stephanopoulos believes the economics of cellulosic ethanol argue strongly for ramping up. Creating a soup-to-nuts system for the fuel would cost a few hundred million dollars, he says. “When you consider the benefits, that’s very reasonable.”