by Jennifer A. Dlouhy 

It’s the holy grail for biofuel developers hoping to coax energy out of algae: Keep the organism fat enough to produce oil but spry enough to grow quickly. 

J. Craig Venter, the scientist who mapped the human genome, just helped Exxon Mobil Corp. strike that balance, with a breakthrough that could enable widespread commercialization of algae-based biofuels. Exxon and Venter’s Synthetic Genomics Inc. are announcing the development at a conference in San Diego on Monday.

They used advanced cell engineering to more than double the fatty lipids inside a strain of algae. The technique may be replicated to boost numbers on other species too.

"Tackling the inner workings of algae cells has not been trivial," Venter said. "Nobody’s really ever been there before; there’s no guideline to go by."

Venter, who co-founded Synthetic Genomics and sequenced the human genome in the 1990s, says the development is a significant advancement in the quest to make algae a renewable energy source. The discovery is being published in the July issue of the journal Nature Biotechnology.

It’s taken eight years of what Venter called tedious research to reach this point.

When Exxon Mobil announced its $600 million collaboration with Synthetic Genomics in 2009, the oil company predicted it might yield algae-based biofuels within a decade. Four years later, Exxon executives conceded a better estimate might be within a generation.

Developing strains that reproduce and generate enough of the raw material to supply a refinery meant the venture might not succeed for at least another 25 years, former chief executive and current U.S. Secretary of State, Rex Tillerson said at the time.

Even with this newest discovery, commercialization of this kind of modified algae is decades away. 

Venter says the effort has "been a real slog."

"It’s to the team’s credit -- it’s to Exxon’s credit -- that they believed the steps in the learning were actually leading some place," he said. "And they have."

The companies forged on -- renewing their joint research agreement in January amid promising laboratory results. 

Exxon declined to disclose how much the Irving, Texas-based company has invested in the endeavor so far. Vijay Swarup, a vice president at ExxonMobil Research and Engineering Co., says the collaboration is part of the company’s broad pursuit of "more efficient ways to produce the energy and chemicals" the world needs and "mitigate the impacts of climate change."

Carbon Consumer
Where Exxon’s chief products -- oil and natural gas -- generate carbon dioxide emissions that drive the phenomenon, algae is a CO2 consumer, Swarup said.

Most renewable fuels today are made from plant material, including corn, corn waste and soybean oil. Algae has long been considered a potentially more sustainable option; unlike those traditional biofuels, it can grow in salt water and thrive under harsh environmental conditions. And the oil contained in algae potentially could be processed in conventional refineries.

The Exxon and Synthetic Genomics team found a way to regulate the expression of genes controlling the accumulation of lipids, or fats, in the algae -- and then use it to double the strain’s lipid productivity while retaining its ability to grow. 

"To my knowledge, no other group has achieved this level of lipid production by modifying algae, and there’s no algae in production that has anything like this level," Venter said in a telephone interview. It’s "our first super-strong indication that there is a path to getting to where we need to go."

Nitrogen Starved
They searched for the needed genetic regulators after observing what happened when cells were starved of nitrogen -- a tactic that generally drives more oil accumulation. Using the CRISPR-Cas9 gene-editing technique, the researchers were able to winnow a list of about 20 candidates to a single regulator -- they call it ZnCys -- and then to modulate its expression.

Test strains were grown under conditions mimicking an average spring day in southern California.

Rob Brown, Ph.D., senior director of genome engineering at Synthetic Genomics, likened the tactic to forcing an agile algae athlete to sit on the bench.

"We basically take an athlete and make them sit on a couch and get fat," Brown said. "That’s the switch — you grab this guy off the track and you put him on a couch and he turns into a couch potato. So everything he had in his body that was muscle, sinew, carbohydrates -- we basically turn that into a butterball. That’s what we’re basically doing with this system.”

Without the change, most algae growing in this environment would produce about 10% to 15% oil. The Exxon and Synthetic Genomics collaboration yielded a strain with more than 40%.

Venter, who is also working on human longevity research, views the development as a significant step toward the sustainable energy he believes humans need as they live longer, healthier lives. The study also is proof, he says, that "persistence pays."

"You have to believe in what you’re doing and that where you’re headed really is the right direction," he said, "and sometimes, like this, it takes a long time to really prove it.”

To contact the reporter on this story: Jennifer A. Dlouhy in Washington at [email protected]

To contact the editors responsible for this story: Jon Morgan at [email protected]

Michael B. Marois

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