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Background  The liberation of acetate from hemicellulose negatively impacts fermentations of cellulosic biomass, limiting the concentrations of substrate that can be effectively processed. Solvent-producing bacteria have the capacity to convert acetate to the less toxic product acetone, but to the best of our knowledge, this trait has not been transferred to an organism that produces ethanol at high yield.    Results  We have engineered a five-step metabolic pathway to convert acetic acid to acetone in the thermophilic anaerobe  Thermoanaerobacterium saccharolyticum . The first steps of the pathway, a reversible conversion of acetate to acetyl-CoA, are catalyzed by the native  T. saccharolyticum  enzymes acetate kinase and phosphotransacetylase.  ack  and  pta  normally divert 30% of catabolic carbon flux to acetic acid; however, their re-introduction in evolved ethanologen strains resulted in virtually no acetic acid production. Conversion between acetic acid and acetyl-CoA remained active, as evidenced by rapid  13 C label transfer from exogenous acetate to ethanol. Genomic re-sequencing of six independently evolved ethanologen strains showed convergent mutations in the  hfs  hydrogenase gene cluster, which when transferred to wildtype  T. saccharolyticum  conferred a low acid production phenotype. Thus, the mutated  hfs  genes effectively separate acetic acid production and consumption from central metabolism, despite their intersecting at the common intermediate acetyl-CoA. To drive acetic acid conversion to a less inhibitory product, the enzymes thiolase, acetoacetate:acetate CoA-transferase, and acetoacetate decarboxylase were assembled in  T. saccharolyticum  with genes from thermophilic donor organisms that do not natively produce acetone. The resultant strain converted acetic acid to acetone and ethanol while maintaining a metabolic yield of 0.50 g ethanol per gram carbohydrate.    Conclusions  Conversion of acetic acid to acetone results in improved ethanol productivity and titer and is an attractive low-cost solution to acetic acid inhibition.    Electronic supplementary material  The online version of this article (doi:10.1186/s13068-015-0257-4) contains supplementary material, which is available to authorized users.

Anaerobic detoxification of acetic acid in a thermophilic ethanologen