Fermentation production of biofuels consumes agricultural crops, which will compete directly with the food supply. As an alternative, photosynthetic cyanobacteria have been proposed as microbial factories to produce various biofuel products directly from solar energy and CO2. However, the biofuel productivity from photoautotrophic cyanobacteria is currently very low, mostly due to the low tolerance of cyanobacterial systems to the toxicity of biofuels. To build a foundation necessary to engineer robust biofuel-producing cyanobacterial hosts, we have applied an integrated approach coupling quantitative iTRAQ proteomics, RNA-seq transcriptomics and metabolomics to reveal the global metabolic responses to several major biofuel products in the model cyanobacterium Synechocystis sp. PCC 6803. In addition, we have applied the tolerance-related gene targets to engineer Synechocystis with improved biofuel tolerance.

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