Jay Keasling
Making Biofuels a Reality
June / July 2010
Volume 8 Number 3
If it wasn’t a defining moment for biofuels research, it certainly was an enlightening one. Holding forth during an interview on “The Colbert Report,” Berkeley microbiologist Jay Keasling took a stab at keeping a straight face and attempting to explain the mission of the Joint BioEnergy Institute, or JBEI, to the irreverent host of the popular Comedy Central TV show.
“That sounds like the name of a New Age cult,” cracks Stephen Colbert. “You don’t sleep under mylar blankets, do you?”
“No, I engineer bacteria to produce fuel from sugar,” replies Keasling.
“You engineer bacteria? Are you a mad scientist?” asks Colbert.
Keasling explains that there are two types of microbes—one that transforms pulp into sugar and another that converts sugar into fuel. Or even drugs. That gets peals of laughter from the audience and elicits raised eyebrows from Colbert. What he means, says Keasling, is that engineered microbes have already yielded an effective antimalaria drug that can be distributed cheaply in the developing world. It turns out, he adds, that this drug is a hydrocarbon, much like the gasoline that powers cars. And the BioEnergy Institute is working on producing microbes that can yield fuel for a variety of engines, including diesel and jet aircraft.
“The same yeast that we use to produce beer and bread can someday fuel cars and planes, using paper and plant waste and debris from cornfields,” he says.
How about animal waste?” interjects the host. “You are talking about cars that run on poop, aren’t you?”
Keasling knows when to play along. “In essence, this is microbial poop, yes,” he acknowledges.
That’s a brave new world,” says Colbert, getting in the last word, as always.
The interview with Keasling aired last year and, in truth, it’s no exaggeration to say that JBEI (pronounced “jay-bay”) is breaking new ground. Opened in 2007 with a grant of $135 million from the Energy Department, the Institute is housed in a glassy four-story building in Emeryville, Calif., not far from Keasling’s home turf at the Lawrence Berkeley National Laboratory, which oversees JBEI. In addition to the Berkeley Lab, the Institute has five other partners: Sandia National Laboratories, Lawrence Livermore National Laboratory, the Berkeley and Davis campuses of the University of California and the Carnegie Institution for Science at Stanford University. JBEI is one of just three DOE-funded bioenergy research centers; the others are Great Lakes Bioenergy Research Center in Madison, Wis., and BioEnergy Science Center in Oak Ridge, Tenn.
With talent from the six Northern California institutions, JBEI has a five-year renewable mission to develop the next generation of biofuels and transfer its breakthroughs to the private sector as quickly as possible. The idea is to use a variety of biomass, from agricultural residue and woody wastes to fast-growing crops of genetically engineered grasses and plants.
Convincing a half-dozen heavyweight partners with widely varying agendas and well-entrenched cultures to work together under one roof was a minor miracle. One might argue that it’s easier to get major league baseball players from competing teams to rub shoulders in the All-Star Game.
Keasling, 46, is the man who pulled it off, convincing the leadership in each institution that cooperating for the common good was vital to the nation’s long-term goal of energy independence.
Keasling, who grew up on a corn and soybean farm in Harvard, Neb., and has a Ph.D. in chemical engineering, has been at JBEI’s helm as chief executive officer from its inception.
Named by Newsweek as “one of the country’s 10 most esteemed biologists,” Keasling is a multitasking dynamo. In addition to his CEO duties, he has been interim deputy director of Berkeley Lab, director of the lab’s Physical Biosciences Division, professor of chemical and bioengineering at UC Berkeley, director of UC Berkeley’s Synthetic Biology Engineering Research Center, and a founder of Amyris Biotechnologies, a renewable products company. His pioneering work in synthetic biology led to the creation of a microbial-based version of the antimalaria drug artemisinin, and for that discovery he was given the first Biotech Humanitarian Award from the Biotechnology Industry Organization. One colleague describes Keasling as a rock star of microbiology.
And he has quite a back-up band of esteemed scientists. The institute operates like a corporation, with a top-down management structure that is atypical of research organizations. “We still encourage the researchers to do the science they want to do, but we’re helping them see the basic vision of JBEI so that we are focused on solving some of the key problems,” says Keasling. The nearly 180 staffers at JBEI retain their institutional affiliations but are distributed throughout the organization in four divisions—much like business units—to explore specific areas of research. They operate cross-functionally in what might be thought of as a kind of biological manufacturing facility.
The Feedstocks Division works on developing plants whose biomass of lignocellulose—the combination of lignin and cellulose that strengthens woody plant cells—can be more efficiently broken down into sugars, which in turn can be fermented to produce biofuels. Researchers in this group are using genetic-engineering tools that were established for rice and Arabidopsis, a small flowering plant that is related to mustard. These are considered ideal for modeling because their growth cycle, from seed to mature plant, is rapid—just weeks or months compared to a year or more for other vegetation. With rice as a model for grasses and Arabidopsis as a model for trees, researchers hope to accelerate the development of new energy crops such as switchgrass. These would provide a more economical alternative to the use of food crops like corn, which is the main source for ethanol. And they could produce the non-ethanol fuels that are needed for aircraft and diesel engines.
When suitable plant materials are identified, the next step is to unlock the sugars for fermentation. So the Deconstruction Division develops new and improved methods of pre-treating lignocellulose to enable its conversion to fermentable sugars. This group is also actively “prospecting” in the rainforests of Puerto Rico for new enzymes and microbes that could be beneficial in processing biomass into biofuels.
And the Fuels Synthesis Division, which Keasling personally directs, is engineering new microbes as an alternative to yeast that can rapidly ferment complex sugars into advanced biofuels. The goal is to have them yield nearly as much energy as petroleum-based fuels. But apart from creating an alternative fuel source for transportation, bioengineered microbes might also be used to replace petroleum ingredients in products such as carpeting, house paint and ceiling tiles. Recently, this group even started experimenting with microbes that can produce a precursor to nylon.
Supporting all three biological research teams is the Technologies Division, which develops processes, hardware and software for the entire organization. These new tools are replacing repetitive, manual work, and some of them are expected to be useful for commercial applications outside of JBEI.
So, housed in one place are all of the elements that can tackle the problems, and Keasling believes that JBEI is the model for biofuels research. DOE Secretary Steven Chu, who is the former director of the Berkeley Lab, has pointed to JBEI as the template for a network of energy research hubs, although there are few regions of the country outside of the San Francisco Bay Area that have so many institutions in close proximity.
“We are building something incredibly different here,” says Keasling. “I’ve been part of academic collaborations before, but the challenge has always been getting people together and having all of the oars in the water at the same time. The way that research is distributed across the country, accomplishing things has been difficult because you have to wait for conference calls and annual retreats. That’s not the way to do coordinated science. Startups don’t run that way, and neither should a research institute. So we’re creating a whole new culture.”
When someone needs a new piece of equipment or a response to a question, it’s just a matter of walking down the hall. Outsiders who tour JBEI can readily see that researchers are thriving in this environment. There is scientific eye candy everywhere, from a greenhouse “growth chamber” of hybrid plants to a special room full of robotics test equipment. “We have access to unbelievable machines,” says Josh Heazlewood, a plant biologist from Perth, Australia, who is director of systems biology. “It’s a fun place to work, no doubt about it.”
Sitting nearby is Nathan Hillson, director of synthetic biology, who had never before interacted with plant biologists but now shares thoughts with them regularly. “People are excited because there are so many resources to pursue your ideas,” he says. “And since we’re all working as a team, we’re focused on the same applications and we have a vested interest in how everyone is doing.”
Production of significant IP has certainly been robust. Among the most promising and near-term discoveries is a genetically engineered strain of Escherichia coli (E. coli) bacteria that can produce fuels and other important fatty acid chemicals directly from biomass without added chemical modifications. E. coli is a well-known microorganism that has a natural ability to synthesize fatty acids. But it is also highly receptive to genetic manipulation, making it an ideal target for biofuels research. The findings surrounding E. Coli originated from Keasling’s fuels synthesis team.
Another important breakthrough allows researchers to quickly evaluate the effectiveness of various ionic liquids in the production of biofuel. These are molten salts that are liquid rather than crystalline at room temperature. Not only can ionic liquids be used to rapidly dissolve lignocellulose in the plant cell walls but they can also help hydrolyze the resulting liquor into sugars. And the researchers are coming up with a process that enables this conversion to occur in a closed loop, by recycling and reusing the non-toxic ionic liquid. This would be a significant improvement over century-old pre-treatment technologies—involving hot water and dilute acids—that were derived from the pulp and paper industry.
With its corporate structure and organization-wide objectives, JBEI is ideally positioned for technology transfer. Under the multi-institutional agreement that formed JBEI, Lawrence Berkeley Lab was designated as the lead for commercialization, so it manages all industry contacts as well as the patent portfolio. So far, the Institute has generated 19 pending patents and 50 published papers, with many more in the wings. “The advances that have come out of JBEI are further along than we thought they would be when we wrote the proposal for this organization,” says Simmons. “We’re proud of what we’ve done so far and excited about what the future holds.”
Companies can engage with the Institute in several ways. Under an Industry Partnership Program, which is overseen by business development manager Pam Seidenman, they can lease space within JBEI and work side-by-side with the government scientists, as two companies are already doing. They can also access JBEI’s IP through license royalties. And they can join an Industry Advisory Committee that provides feedback on JBEI’s research programs.
By early next year, private enterprise will have another reason to look in on JBEI. As a result of an $18 million DOE grant under the Recovery Act, the Berkeley Lab will build an advanced biofuels process development facility that will cover half of one floor below JBEI. This is expected to expedite commercialization of next generation biofuels by providing larger quantities for industry-scale experimentation. The Advanced Biofuels Process Development Unit will be open to other institutions as well as to industry. Here, researchers will be able to manufacture enough fuel in volume so that tens of liters can be available for lab and road engine testing.
Further, Keasling has a starter grant from the National Science Foundation to establish what he says is a world first: a biofab—essentially a store—with an online catalog of biological parts. “We want to make biotechnology like the microelectronics industry, that is, build biological components that are standardized so that people can use them in assembling devices,” he says. The biofab would stock an inventory of enzymes, microbes and biofuels, not unlike the DNA synthesis vendors that offer ship-to-order genes. It would offer largely open-source technology with few if any licensing strings attached.
But turning science into a commodity like transportation fuel will take more than scientific discoveries and proactive outreach to industry, in the view of Harvey Blanch, JBEI’s chief science and technology officer. “It really comes down to cost,” he says. “We’re probably never going back to cheap fossil fuels, but without some legislative support it will be a tough battle for biofuels to compete. Even if we could produce it for something like twice the price of gasoline, there are no operating facilities for biomass right now.” What would be needed, he says, is a government-subsidized production network that utilizes locally based and widely dispersed collectives for fermentation, which would be a sea-change from the centralized system of petroleum refineries.
“It will take a dedicated mindset from Congress to make biofuels a reality,” says Blanch. “Science will have to leap ahead of politics.”
Ken Castle reports from California for Innovation.
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