A multitude of concerns that include climate change, political instability, and depletion of petroleum resources has recently ignited renewed interest in fossil fuel alternatives (1). As a result, micro-bial systems have been extensively explored and successfully used for the biosynthesis of some biofuels, most notably ethanol (2, 3). Higher-chain alcohols, however, offer several advantages compared with ethanol, such as higher energy density and lower water solubility (4). Despite this, the biosynthesis of such alcohols remains a daunting task, with the possible exception of 1-butanol. A new paradigm is now emerging, however, as evidenced in a recent issue of PNAS by the work of Liao and cowork-ers at University of California, Los Angeles (5). Their work demonstrates the construction of nonnatural metabolism that allows the biosynthesis, for the first time, of an array of alcohols not readily produced by microorganisms. In the past, metabolic engineering efforts have exclusively focused on rewiring native metabolic pathways toward a metabolic pathway of interest (6).
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