|The UCLA approach shifts part of the bacteria’s biosynthetic pathway to alcohol synthesis. Various 2-keto acid precursors lead to corresponding alcohols through 2-ketoacid decarboxylase and alcohol dehydrogenase. Click to enlarge.|
Researchers at UCLA have genetically modified Escherichia coli to produce efficiently several higher-chain alcohols from glucose, including isobutanol, 1-butanol, 2-methyl-1-butanol, 3-methyl-1-butanol and 2-phenylethanol. A description of the work appears in the 3 January issue of the journal Nature.
Instead of relying on fermentation for the production of the alcohols, the UCLA approach—developed by professor of chemical and biomolecular engineering James Liao, postdoctoral fellow Shota Atsumi and visiting professor Taizo Hanai—leverages E. coli’s highly active amino acid biosynthetic pathway by shifting part of it (its 2-keto acid intermediates) to alcohol synthesis. In particular, the research team achieved high-yield, high-specificity production of isobutanol from glucose.
These [higher-chain] alcohols are typically trace byproducts in fermentation. To modify an organism to produce these compounds usually results in toxicity in the cell. We bypassed this difficulty by leveraging the native metabolic networks in E. coli but altered its intracellular chemistry using genetic engineering to produce these alcohols.—James Liao
This new strategy opens an unexplored frontier for biofuels production, both in E. coli and in other microorganisms.
The ability to make these branched-chain higher alcohols so efficiently is surprising. Unlike ethanol, organisms are not used to producing these unusual alcohols, and there is no advantage for them to do so. The fact that they can be made by E. coli is even more surprising, since E. coli is not a promising host to tolerate alcohols. These results mean that these unusual alcohols in fact can be manufactured as efficiently as what evolved in nature for ethanol. Therefore, we now can explore these unusual alcohols as biofuels and are not bound by what nature has given us.—James Liao
Compared to ethanol, higher-chain alcohols have energy densities closer to gasoline, are not as volatile or corrosive, and do not readily absorb water. Furthermore, branched-chain alcohols, such as isobutanol, have higher-octane numbers, resulting in less knocking in engines. Isobutanol or C5 alcohols have yet to be produced from a renewable source with yields high enough to make them viable as a gasoline substitute. The approach taken by the UCLA team offers the promise of much higher yields.
UCLA has licensed the technology through an exclusive royalty-bearing license to Gevo Inc., a Pasadena, Calif.-based company founded in 2005 and dedicated to producing biofuels. Liao has joined Gevo’s scientific advisory board. In this role, he will continue to provide technical oversight and guidance during the commercial development of this technology.
The research was supported in part by the UCLA–Department of Energy Institute for Genomics and Proteomics and the UCLA–NASA Institute for Cell Mimetic Space Exploration.
Shota Atsumi, Taizo Hanai & James C. Liao, “Non-fermentative pathways for synthesis of branched-chain higher alcohols as biofuels”, Nature 451, 86-89 (3 January 2008) | doi:10.1038/nature06450