1. NATURE BIOTECHNOLOGY VOLUME 33 NUMBER 11 NOVEMBER 2015 1123
mercial plant to open in 2018, promising up to
10,000 barrels of ‘green crude oil’ per day. But
algae also typically require large growing areas,
and are harvested and processed in batches to
remove their valuable oils, which significantly
increases costs.
To overcome these constraints, some com-
panies are turning to simpler organisms.
“Cyanobacteria make a good microbiological
factory for chemical and fuel production—
they’re the most energy-efficient organisms on
Earth,” says Dannenberg. These photosynthetic
bacteria naturally convert CO2 into pyruvate,
a precursor to various valuable chemicals.
Cyanobacteria excrete these chemicals as they
grow inside bioreactors, allowing manufactur-
ers to extract the products continuously with-
out harvesting the microbes.
Joule Unlimited of Bedford, Massachusetts,
has taken genes from bacterial DNA
sequences in the public database GenBank
to optimise the industrial fitness of cyano-
bacteria. The company modified strains of
Synechococcus to overexpress the pyruvate
decarboxylase and alcohol dehydrogenase
enzymes that convert pyruvate into ethanol.
The organisms can incorporate one or more
of these genes to produce different catalysts,
each optimized to convert CO2 into fuels of
chemicals. The company aims to begin com-
mercial production in 2018. Rival company
Algenol in Fort Myers, Florida, is already
using a cyanobacterium host cell carrying a
genetically enhanced plasmid encoding both
enzymes in the ethanol pathway to produce
over 8,000 gallons of ethanol per acre per year
at a demonstration facility in New Mexico,
more than ten times the typical yield of a corn
ethanol producer.
Joule’s CSO, Dan Robertson, admits that the
commercial prospects for their ethanol—as
withanybiofuel—couldbehamperedbylowoil
prices. That is one of the reasons why Phytonix
has developed a Synechococcuscyanobacterium
that secretes n-butanol. The company also gave
it an engineered proton channel that acts as a
switch—adding an undisclosed chemical to the
brew shifts the microbe from its normal growth
phase into butanol production.
In addition to being an alternative to petro-
leum, butanol is valuable as a raw material for
paints and synthetic rubber, which makes it less
vulnerable to oil price fluctuations. “This hasn’t
been done before because the science wasn’t
there,” says Dannenberg. “Synthetic biology has
allowed scientists to leverage photosynthesis
and build on it to solve some very significant
global challenges.” The process currently oper-
ates only at bench scale, but the company plans
Biotech tools are helping industrial manu-
facturers convert CO2 into useful products,
delegates were told at a conference in late
September on Carbon Dioxide as Feedstock for
Fuels, Chemistry and Polymers held in Essen,
Germany. Bio-based solutions—developed
through genetic engineering, high-throughput
screening and synthetic biology—are muscling
in on what has been traditionally a chemistry-
based industry. Bruce Dannenberg, founder
and CEO of Phytonix in Black Mountain,
North Carolina, a company developing bio-
based carbon capture and utilization (CCU)
technologies, says that just a few years ago,
conferences dedicated to CO2 utilization would
have been dominated by electrocatalytic and
thermochemical approaches. “There has been
a dramatic shift,” he says.
The result is a plethora of demonstration
plants around the world showing that microbes
can produce fuels and feedstock chemicals
from CO2 emissions. “The list is growing—
people are realizing that this can be a useful
approach,” says Jennifer Holmgren, CEO of
bio-CCU company LanzaTech in Skokie,
Illinois.
The chemical industry already re-uses about
200 million metric tons of CO2 per year. Much
of it is turned into urea by the Bosch-Meiser
process, developed in 1922. That, however, is
peanuts by comparison with the biosphere’s
capabilities: photosynthesis helps to convert
about 100 billion metric tons of the gas into
biomass every year (J. Bioprocess. Biotech. 4,
155, 2014).
Industrial processes can also generate use-
ful molecules by direct biological conversion
of CO2. Take algae. Companies like Sapphire
Energy and Cellana, both based in San Diego,
use autotrophic algae—which thrive on noth-
ing more than light, CO2 and a broth of nutri-
ent minerals—to make lipids for conversion
into biodiesel, or high-value chemicals such
as omega-3 fatty acids (Nat. Biotechnol. 31,
870–873, 2013). Large demonstration facilities
are running, and Sapphire expects its first com-
Industrial biotechs turn greenhouse gas into feedstock opportunity
Engineered cyanobacteria act as photobiocatalysts to produce fuel. In the laboratory (top) and soaking
up the sun in Joule’s demonstration plant in New Mexico (bottom).
MarkPeplow
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2. 1124 VOLUME 33 NUMBER 11 NOVEMBER 2015 NATURE BIOTECHNOLOGY
soluble bicarbonate. In these conditions,
carbon extraction is cheaper and uses more
benign solvents, compared with today’s energy
intensive processes involving potentially toxic
amine solvents. The reverse reaction to free
CO2 is also faster using this biocatalyst.
Codexis researchers used directed evolu-
tion to design a highly specific enzyme for
carbon capture. They genetically engineered
carbonic anhydrase genes into Escherichia
coli, and introduced mutations that altered
amino acid sequences around the outside
of the enzyme. High-throughput screening
identified the toughest mutants, and their
beneficial mutations were incorporated
into the next round of evolution. After nine
rounds, Codexis had screened about 50,000
mutants and produced an enzyme that could
withstand the harsh conditions of carbon
capture for weeks without its performance
suffering (Proc. Natl. Acad. Sci. USA 111,
16436–16441, 2014). The process demanded a
degree of automation and data crunching that
was only recently possible, says Oscar Alvizo,
part of the Codexis team: “I don’t believe this
work could have been done 5 years ago.”
CO2 Solutions has been using a simi-
lar enzyme at a pilot plant in Salaberry-­­
all the steel mills in China used this technol-
ogy, it would offer emissions cuts equivalent to
taking 11 million cars off the road.
Holmgren has encountered initial skepti-
cism from some of the heavy-industry com-
panies that LanzaTech partners with. “You go
to someone at a steel plant and ask them to
play with microbes, and they go, ‘Oh really?’,”
she says, laughing. But unlike conventional
chemical approaches to CCU, which tend to
require high-pressure and high-temperature
conditions that are only economical at a large
scale, bio-CCU plants can be much smaller
and less energy-intensive, making them easier
to co-locate with factories. “We don’t believe
that the future of energy is in large centralized
facilities,” says Holmgren.
The dirty carbon in a fossil-fuel plant
poses a different set of challenges. Here,
too, biotech methods are delivering carbon
capture solutions in the form of biocataly-
sis—using enzymes as an alternative to tra-
ditional chemical reactions (Nat. Biotechnol.
31, 95–96, 2013). CO2 Solutions of Quebec
City, Quebec, Canada, partnered with bio-
tech company Codexis of Redwood City,
California, to develop an enhanced carbonic
anhydrase enzyme that transforms CO2 into
Around the world in a month
KENYA
Egerton University in collaboration with
China’s Nanjing Agricultural University
is building a crop molecular laboratory in Nakuru to
help solve problems of low crop productivity. Once
the laboratory receives National Biosafety Authority
clearance, it plans to begin developing genetically
modified crops tailored to Kenyan farming practices.
ARGENTINA
Argentina’s
government asks
citizens for their opinions on
genetically modified crops.
The Agriculture, Livestock
and Fisheries Ministry is
soliciting public comments
on Monsanto’s herbicide-
resistant soy. Results from
this consultation, the first in
20 years, may spur revisions
in its report on agricultural
biotech.
IRAN
Danish biotech Novo Nordisk invests $78 million to
build a manufacturing plant in Iran expected to come
online in 2020. The company had been in negotiations with Iran’s
Food and Drug Administration since before the Islamic Republic
reached a nuclear deal with the West in July. The facility will
produce Novo Nordisk’s FlexPen insulin devices.
AUSTRALIA
The Australian Court of Appeal rules
that farmers of genetically modified
(GM) crops should not be limited in their
operations to accommodate nearby organic
farmers. The decision comes after an organic
farmer filed a case against his neighbor who
was planting GM canola, leading to his loss of
organic certification.
ROMANIA
Romania joins a minority of
EU countries in allowing the
cultivation of GM crops under a law that
permits member states to decide whether or
not to grow the crops. Nineteen of the EU’s
28 member states had applied to keep GM
crops out of all or part of their territories by
the October 4 deadline.
Map:©iStockphoto;Flags:JelenaZaric/Hemera/Thinkstock
to build a demonstration plant by the end of
next year that will produce up to 1,000 gallons
per year.
Rather than inserting a new metabolic
pathway into an organism, LanzaTech has
optimized Clostridium autoethanogenum,
a bacterium that naturally makes acetate
(chemically similar to ethanol). The com-
pany ramped up the bacteria’s output by using
directed evolution, a technique that involves
successive rounds of genetic mutation, with
the most beneficial alterations taken forward
at each stage. The clostridia feed on CO2 and
hydrogen, or straight carbon monoxide—a
waste gas produced by steel plants and petro-
chemical facilities , which is typically burned
to produce CO2.
LanzaTech already runs several clostridia
demonstration plants on carbon monoxide,
including one in partnership with Shougang
Steel near Beijing that is producing 100,000
gallons of ethanol per year. The company is
now building a plant with the steel-maker
ArcelorMittal based in Ghent, Belgium that
should produce up to 47,000 tons of ethanol
per year after it opens in 2017. The first CO2/
hydrogen demonstration plant will be com-
pleted next year. Holmgren estimates that if
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3. NATURE BIOTECHNOLOGY VOLUME 33 NUMBER 11 NOVEMBER 2015 1125
Sexed-up beer
One Belgian
laboratory’s Friday
evening beer fest
has ended with a
paper describing
how to inject
flavor into lagers
by encouraging
some sexual action
between yeasts.
Kevin Verstrepen,
Stijn Mertens and
collaborators at
VIB laboratory for
Systems Biology
in Leuven showed
with genetic
studies that most lager fermentation results from a hybrid species of two parent yeasts—
Saccharomyces cerevisiae, and S. eubayanus. Because these two species are so different,
crossing them to make more diverse lagers has been unsuccessful. At least, so far. The
researchers describe how they optimized growing conditions to foster mating between the
two yeasts, which resulted in hundreds of new lager strains (Appl. Environ. Microbiol.,
doi:10.1128/AEM.02464-15, 25 September 2015). Of the 31 they tested in small-scale
beer fermentors, only 10 performed well in terms of fermentation speed and flavor. Two,
in particular, fermented even faster and produced novel aroma profiles compared with
commercially available lager yeasts.
the technology into more widespread use. For
example, mandatory quotas to blend ­aviation
fuel with 5% of fuel from CCU sources would
­create a valuable market to help fledgling
businesses. “That would be a big step, because
the aviation industry has no idea how to
reduce its CO2 emissions,” says Carus.
Even so, Tuck Seng Wong, a CCU
researcher at the University of Sheffield, UK,
thinks these approaches are still preferable
to pumping waste CO2 into porous rock for-
mations deep underground to capture and
retain excess carbon. CCU plants can pay
for themselves through the chemicals they
produce. In contrast, burying CO2 deep
underground “is analogous to sweeping the
problem under the carpet.”
Mark Peplow Cambridge, UK
de-Valleyfield, Quebec, that captures 10
metric tons of CO2 per day. Crucially, the
enzyme allows them to use smaller tem-
perature swings to absorb and release CO2.
“Compared with other industrial-scale car-
bon capture systems, that means we have the
lowest capture cost right now,” says Louis
Fradette, chief technology officer of CO2
Solutions.
The success of bio-based CCU systems
will ultimately depend on economics, says
Michael Carus, head of the Nova Institut
in Hürth, Germany, an interdisciplinary
research center, which organized the Essen
conference. “They are not price-competitive
yet—but the same is true of biofuels,” he says.
At the conference, delegates discussed
what sort of market incentives might pull
CHROMORANGE/Tscherwitschke/AlamyStockPhoto
First Rounders Podcast:
William Rutter
Bill Rutter is founder, chairman and CEO of Synergenics, which manages
a consortium of biotech companies. He was also a founder of Chiron and
is credited with bringing the University of California at San Francisco to its
prominent position in life sciences research. His discussion with Nature
Biotechnology covers building out the labs at UCSF, sequencing the hepatitis
C virus and his short stint in the Navy.
http://www.nature.com/nbt/podcast/index.html
N E W S
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