Herein we report the discovery of aA u I -DNA hybrid catalyst that is compatible with biological media and whose reactivity can be regulated by small complementary nucleic acid sequences.T he development of this catalytic system was enabled by the discovery of an ovel Au I -mediated base pair.W ef ound that Au I binds DNAc ontaining C-T mismatches.Inthe Au I -DNAcatalystslatent state,the Au I ion is sequestered by the mismatchs uch that it is coordinatively saturated, rendering it catalytically inactive.U pon addition of an RNAo rD NA strand that is complementary to the latent catalystso ligonucleotide backbone,c atalytic activity is induced, leading to as evenfold increase in the formation of af luorescent product, forged through aA u I -catalyzed hydroamination reaction. Further development of this catalytic system will expand not only the chemical space available to synthetic biological systems but also allow for temporal and spatial control of transition-metal catalysis through gene transcription.The use of biocatalysis in synthetic chemistry is emerging as ap owerful strategy for the construction of complex molecules. [1] Protein enzymes,u tilized in isolated form, [2,3] as part of constructed artificial pathways, [4,5] or encapsulated within cells programmed to express them, [6,7] often form reaction products efficiently and stereoselectively under mild conditions.W hile many of the recently developed biocatalytic transformations are mechanistically similar to native biochemical processes,s everal reported systems feature distinctly abiotic transformations,w here the products of the reactions arise through am echanism hitherto unknown in biology.E xamples include Ru-catalyzed olefin metathesis reactions in the artificial active site of an evolved streptavidin protein [8] and Ir-a nd Fe-catalyzed metal carbenoid and nitrenoid insertion reactions from evolved P450 enzymes. [9] In these systems,a biotic chemical reactivity is developed through directed evolution, [10] construction of novel metalloenzymes via transmetalation reactions, [11] aposttranslational metalation, [12] or some combination thereof. [13] It is doubtless that as these strategies improve,t he availability of protein enzymes that catalyze novel abiotic transformations will advance in unison. However,c hemical concepts allowing for control of biocatalytic reactions by biological stimuli, ag oal that would lead to advances in synthetic biology and chemical biology,h ave yet to be explored fully. [14,15] Inspired by current hypotheses concerning the role of ribozymes in biogenesis, [16] the stimuli responsiveness of riboswitches and molecular beacons,and the well-established propensity of late transition metals to bind nucleic acids in asequence-selective manner, [17,18] our group recently became interested in the development of biocatalytic systems composed of nucleic acids and transition metals that mediate chemical reactions.H ere,w ee nvisioned the application of metal-mediated base pairs [19] (MMBPs) comprising catalytically relevant transi...

Here we report the discovery of a Au(I)-DNA hybrid catalyst that is compatible with biological media and whose reactivity can be regulated by small complementary nucleic acid sequences. The development of this catalytic system was enabled by the discovery of a novel Au(I) metal-mediated base pair. We find that Au(I) binds selectively to double stranded DNA containing C–T mismatches. In the Au(I)-DNA catalyst's latent state, the Au(I) ion is sequestered by the mismatch such that it is coordinatively saturated, rendering it catalytically inactive. Upon addition of an RNA or DNA strand that is complementary to the latent catalyst's oligonucleotide backbone, catalytic activity is induced leading to a 7-fold increase in formation of fluorescent product, forged through a Au(I)-catalyzed hydroamination reaction. Further development of this catalytic system will allow for temporal and spatial control of transition metal catalysis through gene transcription.