Nuria Mimbrero-Pelegri

Enzyme engineering has relied on directed evolution, which screens thousands of variants even though fewer than 5% of single mutations are beneficial. REXzyme recasts enzyme design as translation: an encoder reads a reaction written in SMILES and a decoder generates an amino acid sequence token by token, after training on about 21 million reaction-enzyme pairs. Steered toward the reverse reaction of formate dehydrogenase, the reduction of CO2 to formate, all 20 designs generated after family-specific fine-tuning and reinforcement-learning alignment expressed as soluble proteins and showed activity, and design C20 reached a specific activity of 80.8 mU/mg, 2.5 times that of wild-type CtFDH.

Enzyme engineering has relied on directed evolution, which screens thousands of variants even though fewer than 5% of single mutations are beneficial. REXzyme recasts enzyme design as translation: an encoder reads a reaction written in SMILES and a decoder generates an amino acid sequence token by token, after training on about 21 million reaction-enzyme pairs. Steered toward the reverse reaction of formate dehydrogenase, the reduction of CO2 to formate, all 20 designs generated after family-specific fine-tuning and reinforcement-learning alignment expressed as soluble proteins and showed activity, and design C20 reached a specific activity of 80.8 mU/mg, 2.5 times that of wild-type CtFDH.