Modular Assembly and Optimization of an Artificial Esterase from Functionalised Surfactants

A strategy for the screening and optimization of an artificial esterase is presented that utilizes the self-assembly of amphiphilic molecules. Unlike conventional approaches that rely on the attachment of key functional groups onto molecular scaffolds or surfaces, the modular assembly of amphiphiles allows a large number of catalytic combinations to be investigated with minimal synthetic effort. In this study, iterative combinatorial screens led to an optimized esterase comprising amphiphiles that act as a nucleophilic catalyst, an oxyanion hole and a metal ion chelator. Cooperativity is observed between the functional headgroups of the amphiphiles, an effect that is diminished when co-assembled with non-functionalized surfactants. Assessment of the catalytic efficiency (kcat/KM) of our optimized catalysts against recently reported artificial esterases shows comparable efficiency, indicating that efficient catalysis is possible with dynamic self-assembled systems despite the absence of pre-defined rigid binding pockets.A strategy for the screening and optimization of an artificial esterase is presented that utilizes the self-assembly of functionalized amphiphilic molecules. The optimized system comprises amphiphiles that act as a nucleophilic catalyst, an oxyanion hole and a metal ion chelator, and demonstrates that efficient catalysis is possible with dynamic self-assembled systems despite the absence of pre-defined rigid binding pockets. image