Biofuel solutions and genetically engineered microbes
MIT’s Kristala Jones Prather says when she was invited to testify before a Senate committee on the topic of biofuels this past summer, “I was a nervous wreck.”
The event went smoothly, though — and also gave her a firsthand look at democracy in action. “The chairman, the ranking minority member, and one other member stayed all day,” says Prather. Others were more selective. “Five minutes before a particular person was due to testify,” she says, “the senator from his or her state would show up.”
Prather’s message to the group was that biofuels have a lot to offer but aren’t a quick fix. Indeed, she said that making high quality and affordable biofuels would require “a systems-based solution.”
That solution will include finding safe, cost-effective ways to turn certain crops or crop residues — poplar trees, the prairie weed called switch grass, and agricultural wastes, among others — into biofuels. As it happens, Prather is in the thick of efforts to set the stage for that development.
The faculty member’s work involves genetically engineering organisms to fulfill roles nature hasn’t chosen them for. One such role is “microbial chemical factory.”
Some organisms have been at this a long time: the beer-yeast connection goes back millennia. But it’s in yeast’s nature to do the fermenting work that yields the alcohol in beer. What’s new about Prather’s approach is that to get the organisms to make something useful — biofuels, drugs, or other products — the microbes she works with must be genetically reprogrammed.
Producing biofuels this way may turn out to be more cost-effective and environmentally respectful than building big chemical processing plants. The obstacles, though, are steep. “We don’t really know whether these microbes are physically capable of doing what we want them to do,” notes Prather.
TEXAS TO MIT
The backdrop for Prather’s current career includes a conversation with a favorite teacher at her Longview, Texas, high school. The teacher asked about her college plans. Prather, a math-science whiz, described her interests, and the teacher told her she should strongly consider MIT. “I’d never heard of it,” notes Prather. But after speaking with MIT alumnus Robert Cargill, a Longview resident, and visiting the campus, she was sold.
The next 14 years would see her earn her bachelor’s degree at MIT and a doctorate at Berkeley, complete a research stint at Merck, and join the MIT faculty.
In trying to turn bacteria into chemical makers, Prather didn’t start with a biofuel as her goal but rather a substance called glucaric acid. “Its most promising use may be as a building block for novel kinds of materials,” she notes.
The researcher’s microbial helper is E. coli. This organism sometimes makes headlines in food-poisoning episodes, but it’s also a common and usually harmless denizen of the human gut, where it aids with tasks like digestion.
If Prather’s group can turn E. coli into a productive maker of glucaric acid, it could open the way, among other possibilities, for creating biofuel-specific microbes. But that first step won’t be easy — as comparing re-engineering a microbe to the task of retrofitting a chemical plant makes clear.
Say the idea is to convert a plant from making chemical A to making chemical B through the installation of a few, but critical, new parts. Executing the same job with E. coli is like working with a factory whose machinery is invisible, and whose response to the installation of any one new piece of gear is highly unpredictable. It also may take you many months of work to find the new parts — in this case, genes — you want to install.
Then there’s the fact that the organisms your new genes come from may favor environments very different from the ones your target microbe likes. “It’s as if your blueprints have to change depending on whether it’s 90° or 50° outside,” says Prather.
The faculty member wants to create E. coli that can turn glucose, a type of sugar, into glucaric acid. It takes three chemical steps, and that means you need three enzymes that are foreign to E. coli. Her group has inserted genes for two of these into the microbe, and those enzymes are productive in lab tests. But that’s still a small step along a pitfall-ridden pathway.
Prather has done experiments where a new gene in E. coli starts making small amounts of the enzyme you want, but where, when you take supposedly proven steps to boost the enzyme’s output, “they have the opposite effect, and the gene stops working.” Still, she’s confident the system will yield glucaric acid.
She further sees biological methods as being critical to a secure energy future — one, moreover, that may take us beyond ethanol, the type of biofuel most in the limelight right now.
Ethanol has many advantages but also some downsides. An example: it mixes easily with water, which means water intrusion could be a problem in terms of piping the fuel over significant distances.
So, one of Prather’s long-term aims is to create microbial chemical-makers that can generate products that no one has even thought of yet. Then — just as oil refineries are able to produce a range of compounds — biorefineries could be configured to produce a range of both biofuels and other chemicals. “It could take a good part of my academic lifetime for all of this to come to fruition,” adds Prather, “but it’s very exciting to be in on the early stages.”