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green diesel fuel every year.

Like ethanol, Amyris’s fuel will be made by fermenting sugar. But company scientists have redesigned yeast so that the microbes process it into combustible hydrocarbons instead of alcohol. That means the competition for its green fuel is not ethanol but diesel made from petroleum and also biodiesels made from vegetable oil or animal fat. Amyris says its fuel has a number of advantages over both. Unlike fossil fuels, it is made from a renewable source. It also contributes less greenhouse gas to the atmosphere: the company calculates that its Brazilian-made diesel will emit about 80 percent less greenhouse gas than conventional diesel. And compared with other biodiesels, its sugar-based fuel will be cheaper to make and will enable engines that use it to run better. Amyris’s CEO, a former oil executive named John Melo, has been negotiating with companies that are looking for a green fuel, including Federal Express, Virgin Atlantic, and General Electric.

Yeast Factory: At Amyris’s demonstration facility in Brazil, hydrocarbons are produced in a fermentation tower.

For many synthetic biologists, diesel is just the beginning. They believe that in principle, they can create microörganisms to produce replacements for any petroleum product. But there are huge risks. Amyris’s yeast strains have proved unexpectedly vulnerable. And as with other biotechnology processes that depend on live microörganisms, no one can say if green diesel production can be scaled up economically from the 1,000-liter batches produced today. “All the forecasts are based on efficiencies of scale for processes that have never been run at those scales,” says ­Noubar Afeyan, CEO of Flagship Ventures in Cambridge, MA, and a cofounder of LS9, a competing synthetic-biology startup. A major challenge is that it “takes hundreds of millions of dollars to prove it, even at medium scale.”

Nine years ago, Amyris’s technology was still a bench project in Keasling’s Berkeley laboratory. Researchers had been looking at ways to coax microörganisms to produce commercially useful products. By adding DNA from plants and bacteria, Keasling’s lab eventually designed new bacteria and yeast cells that could make large quantities of isopentenyl pyrophosphate. With its five carbon atoms, the chemical is a sort of Lego block of the natural world; from it, plants and animals build isoprenoids, members of a large class of molecules that includes the anticancer drug taxol, vitamin E, and scents such as those of grapefruit and the pheromones of female cockroaches.

Keasling knew the invention was valuable, and in 2001 he filed the first patent application of his career. “We wanted to apply the tools to a real problem,” he says. The chance came in 2004, when the Bill and Melinda Gates Foundation decided to donate $42.6 million to a project that would manufacture the antimalaria drug artemisinin with the aid of Keasling’s made-to-order microbes.

Artemisinin is currently derived from the sweet wormwood plant, grown mostly in Africa and Asia. Supply of the drug is unsteady, and prices swing wildly; they reached $1,100 a kilogram in 2006. By using genetically modified yeast to produce it from sugar, Keasling’s approach promised to solve the supply problem and dramatically cut the price. With its chance of saving thousands–perhaps millions–of people who might otherwise die of malaria, the project has become a symbol of synthetic biology’s potential to change the world for the better. The Gates money paid for the rapid expansion of Amyris, which Keasling and three of his postdocs founded to carry out the malaria project. By late 2005, says Amyris’s chief technical officer, Neil Renninger, some at the company were spending “nights and weekends” thinking about what other problems their technology could solve.

Inside a fermenter, genetically modified yeast metabolizes sugar and produces farnesene, a fragrant hydrocarbon oil.

Amyris estimates that the isoprenoid family includes some 50,000 different types of molecules, so it was far from clear where to focus next. “When we began pitching the VCs, we said there are some drugs we think are interesting, and nutraceuticals, and even fuels–what do you think?” recalls Renninger. But it was hard to find a project as meaningful to Amyris’s scientists as malaria. “This was really a culture of people that want to save lives and not make a lot of money,” he says. “So when you throw making grapefruit flavor in front of them–well, it’s not too interesting.”

Things started changing by mid-2006, when two of Silicon Valley’s best-known venture capital firms, Kleiner Perkins Caufield and Byers and green-energy specialist Khosla Ventures, offered to invest $20 million in the company. The U.S. Congress had passed renewable-fuel mandates in 2005, setting off a wave of speculative investment in all sorts of biofuels. Geoffrey Duyk, a managing director at TPG Biotech, which also put money into the company, recalls that once Amyris accepted the funds, the investors “came in and moved the focus to fuels.”

The investors began courting Melo, then head of British Petroleum’s North American fuels business, to be Amyris’s CEO. Melo was running what he calls a “nice little business” involving huge truck fleets and scores of terminals, generating $34 billion in revenue. When a recruiter first called him about a biotech company with a malaria project, he recalls, “My reaction was, ‘You have got to be kidding. I am a fuels guy,

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Credits: Noah Friedman-Rudovsky
Video by Noah Friedman-Rudovsky, edited by JR Rost

Tagged: Biomedicine, Energy, Amyris

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