Nothling, Mitchell DXiao, ZeyunHill, Nicholas SBlyth, MitchellBhaskaran, AyanaSani, Marc-AntoineEspinosa-Gomez, AndreaNgov, KevinWhite, JonathanBuscher, TimSeparovic, FrancesO'Mara, MeganCoote, MichelleConnal, Luke2020-08-262020-08-262375-2548http://hdl.handle.net/1885/209059The remarkable power of enzymes to undertake catalysis frequently stems from their grouping of multiple, complementary chemical units within close proximity around the enzyme active site. Motivated by this, we report here a bioinspired surfactant catalyst that incorporates a variety of chemical functionalities common to hydrolytic enzymes. The textbook hydrolase active site, the catalytic triad, is modeled by positioning the three groups of the triad (-OH, -imidazole, and -CO2H) on a single, trifunctional surfactant molecule. To support this, we recreate the hydrogen bond donating arrangement of the oxyanion hole by imparting surfactant functionality to a guanidinium headgroup. Self-assembly of these amphiphiles in solution drives the collection of functional headgroups into close proximity around a hydrophobic nano-environment, affording hydrolysis of a model ester at rates that challenge α-chymotrypsin. Structural assessment via NMR and XRD, paired with MD simulation and QM calculation, reveals marked similarities of the co-micelle catalyst to native enzymes.Funding from the U.S. Army International Technology Centre Pacific ITC-PAC FA5209-14-C-0017 and the Australian Research Council (ARC)(DP200100535) is gratefully acknowledged (to L.A.C. and M.L.O.). M.D.N. and L.A.C. acknowledge the Australia Science Endowment Fund (SIEF) for a John Stoker postgraduate Scholarship, as well as an Endeavour Research Fellowship and Australian Nanotechnology Network Overseas Travel Fellowship (to M.D.N.). M.L.C. acknowledges financial support from the ARC Centre of Excellence for Electromaterials Science (CE140100012), an ARC Laureate Fellowship (FL170100041), and supercomputing time from the National Computational Infrastructureapplication/pdfen-AUCopyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Sciencehttps://creativecommons.org/licenses/by-nc/4.0/202010.1126/sciadv.aaz0404Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC)