A Polymeric Approach to Designing Semisynthetic Enzymes.

Incorporating synthetic chemicals into natural enzyme scaffolds to create semisynthetic enzymes is a promising strategy for achieving novel enzymatic functions. However, limitations such as low efficiency and a lack of control have hindered their industrial application. In this study, we propose a polymeric approach to designing semisynthetic enzymes by integrating ruthenium-containing polymers with the transaminase (ATA) scaffold via a "grafting from" copolymerization method. Initially, we combine noncatalytic proteins with polymers acting as dehydrogenases to convert acetophenone to (R)-1-phenylethanol with 99% conversion and 94% enantiomeric excess (ee). Furthermore, a polymeric semisynthetic ATA, referred to as "PolySemiATA," is created by combining ATA and polymer catalysts using the same methodology. Remarkably, PolySemiATA not only retains the natural catalytic activity of enzymes but also enables an efficient one-pot cascade from (S)-1-phenylethylamine to (R)-1-phenylethanol with 99% conversion and 93% ee. Furthermore, PolySemiATA displays a significant advantage in recycling, surpassing the performance of mixtures composed of ATA and polymer catalysts. This study demonstrates the concept of a polymeric approach for designing semisynthetic enzymes, holding potential for producing high-value chemicals with various enzymes combined with different catalytic modular polymers to meet the demands of advanced synthesis.