As the global demand for biofuels continues to grow, biofuels production using microorganisms has become one of the most attractive approaches of making biofuels economically viable and cost-effective. Thanks to the advancement of new technologies in molecular biology such as phenotype engineering, a microorganism can be tailor-made to increase its productivity of a certain substance by optimizing genetic and regulatory processes within a cell. The engineering of desired phenotypes in microorganisms often requires the complete reprogramming of innate gene expression networks, a process that necessitates multigenic transcriptional coordination. Lee and coworkers recently developed novel artificial transcription factors (ATFs) to elicit simultaneous multiple gene modifications, thus inducing new phenotypic variations in microorganisms (Lee et al., 2008. Nucleic Acids Res 36:e102). Here, they applied ATFs to reconstitute genetic networks and thus to engineer phenotypes in E. coli to be more suitable for the production of biofuels, especially biobutanol. This research is an important step on the road to designing a microorganism with a new and improved property thus generating a microbial factory for biofuels production. Page 742