Molecular computing based on enzymes or nucleic acids has attracted a great deal of attention due to the perspectives of controlling living systems in the way we control electronic computers. Enzyme-based computational systems can respond to a great variety of small molecule inputs. They have the advantage of signal amplification and highly specific recognition. DNA computing systems are most often controlled by oligonucleotide inputs/outputs and are capable of sophisticated computing as well as controlling gene expressions. Here, we developed an interface that enables communication of otherwise incompatible nucleic-acid and enzymecomputational systems. The enzymatic system processes small molecules as inputs and produces NADH as an output. The NADH output triggers electrochemical release of an oligonucleotide, which is accepted by a DNA computational system as an input. This interface is universal because the enzymatic and DNA computing systems are independent of each other in composition and complexity.Modern silicon-based analog/digital computer technology has been one of the most successful and influential transformative developments in recent history. At the same time, natural biological molecules (e.g., nucleic acids and proteins) are organized in complex communicating networks responsible for growth of all living creatures through metabolism and reproduction. It was suggested that application of the well-developed computational approach to biological molecules may open new chapters in understanding biological signaling, neuron communication, [1] and cancer development, [2] as well as in improving diagnosis of infectious diseases and genetic disorders.[3] Indeed, biomolecular information processing has been an active research field [4] in the general framework of chemical [5] unconventional computing. [6] In this research area, DNA computing [4a-e] and enzyme-based computing [7] have received exceptional attention. DNA computing is believed to be a potential alternative to electronic computers [8] for some computational tasks, due to the advantage of massive parallel data processing, [9] a straightforward design of relatively complex circuits, [10] and affordability. Among the most obvious applications of DNA-based logic circuits is the analysis of genetic alterations that can be transformed into clinical testing of infectious and genetic diseases. [2, 3] Despite advances in the development of in vitro selection, functional DNAs are still limited in the diversity and efficiency of catalytic reactions and are inferior to proteins in terms of affinity and diversity of ligands that DNA can recognize. [11,12] At the same time, enzymes are proven to be selective and sensitive receptors; they are known as the best catalysts, enabling rate enhancement up to 10 17 fold in comparison with uncatalyzed reactions.[13] However, enzyme-based computing was experimentally limited to the systems mimicking operation of only a few concatenated logic gates, [7] and the network complexity was restricted by enzym...