The team used directed evolution to improve enzyme performance. A second enzyme variant, ASA1.5, enabled the formation of molecules containing all-carbon quaternary stereocentres, structures that can be challenging to synthesise selectively. The researchers demonstrated that the engineered enzymes could work with a broad range of reaction partners, including substituted furans, indoles, pyrroles, cyanoesters, diketones, ketoesters, anilines and isatins. Across the reactions examined, the enzymes generated a single major product with no observable by-products other than the released leaving group used for monitoring the reaction. The study highlights how engineered protein catalysts can provide new ways to access molecular structures that are difficult to produce using established small-molecule catalysts.