The ability to maximize the use of available nucleic acid sequence space would have been crucial during the presumed RNA world and confers selective advantage in many contemporary organisms. One way to access sequence space at a higher density would be to make use of both strands of a duplex nucleic acid for the production of functional molecules. As a demonstration of this possibility, two pairs of nucleic acid enzymes were engineered to be perfect complements, each with the capacity to adopt a distinct structure and catalyze a particular chemical transformation. Both members of each pair of enzymes exhibited nearly the same level of activity as the canonical form of the corresponding catalytic motif. The ability to generate functional nucleic acids encoded by both strands of a duplex has implications for the evolution of catalytic nucleic acids and the prospects for realizing maximum functionality from a given genetic sequence.