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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 phero-
mones 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 thou-
sands---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 o cer, Neil Renninger, some at the
company were spending "nights and weekends" thinking about
what other problems their technology could solve.
Amyris estimates that the isoprenoid family includes some
50,000 di erent 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 Val-
ley's best-known venture capital firms, Kleiner Perkins Caufield
and Byers and green-energy specialist Khosla Ventures, o ered to
invest $20 million in the company. The U.S. Congress had passed
renewable-fuel mandates in 2005, setting o a wave of speculative
investment in all sorts of biofuels. Geo rey 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 Petro-
leum'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 rev-
enue. 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, so what do I care?' "
As he learned more about synthetic biology and met Amyris's
scientific sta , Melo changed his mind. Fuels are the largest of all
businesses by revenue, but as a percentage of profits, oil compa-
nies spend only tiny sums on R&D and almost nothing on basic
research. Melo decided his old industry was ripe for change. "The
ability to modify microbes [means] we can be the Microsoft of fuels
and chemicals, where we are in e ect writing the software that goes
into the fermentation tank," he says. "That, to me, was game chang-
ing." Melo directed the company to work on diesel, the world's most
widely used transportation fuel and one that is often in short sup-
ply. Producing the right type of molecule proved surprisingly easy.
Within six weeks, the scientists had switched a single enzyme in
their artemisinin-producing bugs and begun producing farnesene,
the oil they had identified as a potential precursor to diesel.
"They look like very di erent projects---one is a medicine and
one is a fuel---but the metabolic route is similar," Collier says. "That
was the big advance of Amyris." Farnesene is a pleasant-smelling
oil that accounts in part for the odor of apple skins. By performing
one additional chemical step, hydrogenation, Amyris can turn the
yeast-produced farnesene into farnesane, a highly combustible
fuel with properties similar to those of diesel.
As a hydrocarbon like diesel and gasoline, farnesane won't be
subject to the problems that have a ected other biofuels, Amyris
is betting. Ethanol, for example, can mix with water, which may
cause trouble when water makes its way into gasoline pipelines.
Plant-derived biodiesels, meanwhile, contain impurities and can
clog engines at low temperatures. Farnesane, on the other hand,
can be simply dropped into the existing fuel distribution network.
It even has an advantage over ordinary diesel: it contains no pol-
But the project will have an impact only if it can be deployed at
a massive scale. And no one is yet sure how well synthetic biology
will work at such scales. Synthetic Genomics, a company started by
FEEDSTOCK A sugarcane plantation near the city of Campinas. Each
acre yields enough sugarcane juice to make 3,000 liters of ethanol.
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