NATURE CHEMICAL BIOLOGY | VOL 10 | MAY 2014 | www.nature.com/naturechemicalbiology 331
perspective
PUBLISHED ONLINE: 17 APRIL 2014|DOI: 10.1038/NCHEMBIO.1509
M
eeting the increasing demand for petroleum by the global
transportation sector has required the deployment of new
extraction technologies, such as enhanced oil recovery and
hydraulic fracturing of shale rock as well as exploitation of resources
such as tar sands and oil shale
1,2
. is transition to unconventional
resources is accompanied by an increase in greenhouse gas (GHG)
emissions 0.5–3 times higher than that of conventional resources
(Fig. 1a)
3
.
e use of natural gas, specically methane, in transportation
should be considered a viable option for reducing petroleum
dependence and GHG emissions associated with the exploitation of
unconventional resources. Globally, natural gas resources that are
technically recoverable with new horizontal drilling and ecient
extraction technologies are estimated at 7.2 × 10
3
trillion
3
(Fig. 1b)
1
.
Estimates for the US range between 0.65 × 10
3
trillion
3
and up to
2 × 10
3
trillion
3
, a quantity capable of supplying the US with 100
years of natural gas at current usage rates
1
. is increased availability
in the US has placed downward pressure on natural gas prices and
created a large price spread between natural gas and petroleum on an
energy-equivalent basis (Fig. 1c).
Methane is not only an energy resource but also a potent GHG,
with a greenhouse warming potential 21 times that of carbon
dioxide over a 100-year period. When converted to CO
2
equivalents,
anthropogenic sources of methane contribute nearly 20% of the
world’s GHG warming potential each year
4
. In addition to emissions,
venting and inecient aring of natural gas produced as a byproduct
of petroleum extraction is responsible for an estimated 5 trillion
3
of
GHG released to the atmosphere worldwide
5
. erefore, technologies
to eectively use methane not only from pipeline sources but also
from smaller, distributed sources should be pursued as eective
means to both produce energy and mitigate GHG warming potential.
Direct use of natural gas as compressed natural gas in the
transportation sector is constrained owing to the inherent low
volumetric energy density of natural gas and the lack of fueling
and end-use infrastructure required for its broader adoption by
light duty vehicles
6
. An alternative means to use natural gas as
a transportation fuel involves gas-to-liquid (GTL) conversion
technologies such as those based on the production of synthesis
gas (syngas, a gas mixture predominately composed of carbon
monoxide and hydrogen) and subsequent conversion via the
Fischer-Tropsch (FT) process (generally approximated as
Rethinking biological activation of methane and
conversion to liquid fuels
Chad A Haynes
1
& Ramon Gonzalez
2
*
If methane, the main component of natural gas, can be eciently converted to liquid fuels, world reserves of methane could sat-
isfy the demand for transportation fuels in addition to use in other sectors. However, the direct activation of strong C-H bonds in
methane and conversion to desired products remains a dicult technological challenge. This perspective reveals an opportunity
to rethink the logic of biological methane activation and conversion to liquid fuels. We formulate a vision for a new foundation for
methane bioconversion and suggest paths to develop technologies for the production of liquid transportation fuels from methane
at high carbon yield and high energy eciency and with low CO
2
emissions. These technologies could support natural gas biocon-
version facilities with a low capital cost and at small scales, which in turn could monetize the use of natural gas resources that are
frequently flared, vented or emitted.
2(n+1)H
2
+ nCO → C
n
H
(2n+2)
+ nH
2
O). Although attractive,
the current GTL-FT approach is a technologically complex,
multistep process involving conversion of methane to syngas,
catalytic conversion of syngas to long-chain hydrocarbons and
subsequent cracking and separation of a broad range of products
for market. e process is encumbered by numerous heat and
pressure changes, all of which require multiple unit operations
that markedly increase technical complexity and capital expenses
(CapEx). ese process demands result in deployment of
exceptionally large-scale facilities to leverage economies of scale
that cannot be eciently scaled down, thus requiring signicant
CapEx for each facility in upwards of $20 billion (Fig. 1d). In
addition, production of liquid fuels through GTL-FT processes
would lead to GHG emissions approximately 50% higher than that
of conventional resources (Fig. 1a).
Enabled by recent developments in enzymatic oxidation of
methane and synthetic biology, this perspective presents the
opportunity to develop industrially relevant biotechnology and
bioprocessing for new GTL technologies. Bio-based approaches to
GTL are anticipated to be less technologically complex and operate
protably on small scales compared to current GTL-FT. Here we
address some of the challenges and technological opportunities for
ecient biological activation of methane and synthesis of liquid fuels.
Bioconversion: low CapEx and high eciency
Biological conversion (bioconversion) processes oer a potential
solution to the large-scale, capital-intensive nature of the GTL-
FT approach. Corn-grain ethanol fermentation is perhaps the
best example of a biological process for fuel production deployed
at commercial scale and hence will be contrasted here to the
aforementioned GTL-FT process. In ethanol fermentation, sugars
are converted to ethanol via a yeast biocatalyst capable of high
metabolic and process eciencies, respectively 97% and 81%,
and with ethanol product specicity greater than 90% (ref. 7).
e bioprocess operates at mild temperatures and can integrate
saccharication and fermentation into a single-unit operation.
Taken together, these features result in a process that is less
technologically complex than GTL-FT and supports small-scale
deployment at signicantly lower CapEx (Fig. 1d). e lower
CapEx of corn-grain ethanol facilities has supported more rapid
and widespread deployment in the US than commercial-scale
1
Booz Allen Hamilton, Washington, DC, USA.
2
Advanced Research Projects Agency–Energy, United States Department of Energy, Washington, DC, USA.
*e-mail: ramon.gonzalez@hq.doe.gov or ramon.gonzalez@rice.edu
npg
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