Building cell factories for the production of advanced fuels

Synthetic biology-based engineering strategies are being extensively employed for microbial production of advanced fuels. Advanced fuels, being comparable in energy efficiency and properties to conventional fuels, have been increasingly explored as they can be directly incorporated into the current fuel infrastructure without the need for reconstructing the pre-existing set-up rendering them economically viable. Multiple metabolic engineering approaches have been used for rewiring microbes to improve existing or develop newly programmed cells capable of efficient fuel production. The primary challenge in using these approaches is improving the product yield for the feasibility of the commercial processes. Some of the common roadblocks towards enhanced fuel production include - limited availability of flux towards precursors and desired pathways due to presence of competing pathways, limited cofactor and energy supply in cells, the low catalytic activity of pathway enzymes, obstructed product transport, and poor tolerance of host cells for end products. Consequently, despite extensive studies on the engineering of microbial hosts, the costs of industrial-scale production of most of these heterologously produced fuel compounds are still too high. Though considerable progress has been made towards successfully producing some of these biofuels, a substantial amount of work needs to be done for improving the titers of others. In this review, we have summarized the different engineering strategies that have been successfully used for engineering pathways into commercial hosts for the production of advanced fuels and different approaches implemented for tuning host strains and pathway enzymes for scaling up production levels.