In this study, the native redox cofactor regeneration system in Escherichia coli was engineered for the production of butyric acid. The synthetic butyrate pathway, which regenerates NAD(+) from NADH using butyrate as the only final electron acceptor, enabled high-yield production of butyric acid from glucose (83.4% of the molar theoretical yield). The high selectivity for butyrate, with a butyrate/acetate ratio of 41, suggests dramatically improved industrial potential for the production of butyric acid from nonnative hosts compared to the native producers (Clostridium species). Furthermore, this strategy could be broadly utilized for the production of various other useful chemicals in the fields of metabolic engineering and synthetic biology. (C) 2012 Elsevier Ltd. All rights reserved.