A non-naturally occurring microbial organism having a methyl ethyl ketone pathway includes at least one exogenous nucleic acid encoding a methyl ethyl ketone pathway enzyme expressed in a sufficient amount to produce methyl ethyl ketone. The methyl ethyl ketone pathway includes a β-ketothiolase, a β-ketovalerate decarboxylase and an enzyme selected from the group consisting of a β-ketovaleryl-CoA hydrolase and a β-ketovaleryl-CoA transferase. Alternatively, the methyl ethyl ketone pathway includes a 2-methylacetoacetyl-CoA thiolase, a 2-methylacetoacetate decarboxylase and an enzyme selected from the group consisting of a 2-methylacetoacetyl-CoA hydrolase and a 2-methylacetoacetyl-CoA transferase. Either pathway can further include a methyl ethyl ketone reductase to produce 2-BuOH. A method for producing methyl ethyl ketone or 2-BuOH includes culturing these non-naturally occurring microbial organisms under conditions, and for a sufficient period of time, to produce methyl ethyl ketone or 2-BuOH.