Defossiling fuel: how synthetic biology can transform biofuel production.

A lthough crude oil production is predicted to peak soon, it is reasonable to assume that unconventional fossil fuel sources can continue to meet society’s increasing energy demands for many decades to come (1). The real challenge is sustainability: stabilizing and reversing global climate change, minimizing political and economic energy volatility, and smoothing the transition from fossil fuels in the distant future. In response to this challenge, many are looking to biotechnology to develop biofuels, such as ethanol, butanol, biodiesel, and hydrogen (H2), in which the energy ultimately derives from photosynthetic capture of sunlight. A fundamental issue with biofuels is efficiency. The pathway from sunlight through natural intermediates to final molecule is long, and biofuel production is perhaps the ultimate metabolic engineering problem (2). This challenge is made even greater by its inherent systems complexity, because any solutionmust be implemented in the context of an energy infrastructure with challenging engineering, economic, political, and environmental realities. Are biofuels sustainable? Consider U.S. transportation fuels, a market poised for impact. Biofuels derive their stored chemical energy from the sun viaphotosynthesis. Biofuel use is therefore a closed carbon cycle, as carbon released during combustion is sequestered during photosynthesis. Solar radiation is clearly a sustainable energy source on human time scales, and U.S. incident solar power ( 2300 TW) (3) greatly exceeds our transportation fuel usage ( 1.0 TW) (Table 1) (4). The reactions of photosynthesis impose a maximal efficiency of 12%, but final yields are significantly lower (2). Terrestrial plant efficiencies for solar to biomass conversion is maximally 2% (e.g., for the rapidly growingMiscanthus (5)), and the subsequent conversion into biofuels is 50% efficient (6). It would therefore require 4.3% of the U.S. land area to meet our transportation energy demands, which corresponds to 22% of current cropland. Thus, in an optimistic approximation (and ignoring social, political, and economic complexities), we can say biofuel production could be sustainable, albeit with significant challenges. These calculations suggest that a biofuelbased energy economy is feasible but that enhancements in the efficiency of any step in energy production would be favorable fromaneconomic and environmental standpoint. The upper bound on efficiency is set by photosynthesis—the challenge is therefore to come as close to this bound as possible. Put another way, how can one optimizemetabolism todirectmaximal flux from one set of metabolites to another, while still maintaining, at least partially, host fitness? Traditional industrial approaches have given us many such successes (e.g., beer) andwill play amajor role, but the tools of systems and synthetic biology promise to deliver a degree of optimization not previously attainable (7). A synthetic-biological redesign of the organisms that produce biofuels has the potential to significantly increase efficiency, *Corresponding author, pamela_silver@hms.harvard. edu.