Engineering for life in toxicity: Key to industrializing microbial synthesis of high energy density fuels

With the growing demand for air transportation combined with global concerns about environmental issues and the instability and lack of renewability of the oil market, microbial production of high energy density fuels for jets (bio-jet fuels) has received more attention in recent years. Bio-jet fuels can be derived from both isoprenoids and fatty acids, and, additionally, aromatic hydrocarbons derived from expanded shikimate pathways are also candidates for jet fuels. Compared to fatty acid derivatives, most of isoprenoids and aromatic hydrocarbons used for jet fuels have higher density energies. However, they are also highly toxic to host microbes. The cytotoxicity induced during the synthesis of isoprenoid or shikimate pathway-derived biofuels remains one of the major obstacles for industrial production even though synthetic and systems biology approaches have reconstructed and optimized metabolic pathways for production of these bio-jet fuels. Here, we review recent developments in the production of known and potential jet fuels by microorganisms, with a focus on alleviating cytotoxicity caused by the final products, intermediates, and metabolic pathways.