AbstractAn aminomutase, naturally catalyzing the interconversion of (S)‐α‐phenylalanine and (R)‐β‐phenylalanine, was converted into an ammonia lyase catalyzing the nonoxidative deamination of phenylalanine to cinnamic acid by a rational single‐point mutation. It could be shown by crystal structures and kinetic data that the flexibility of the lid that covers the active site decides whether the enzyme acts as a lyase or a mutase. An Arg92Ser mutation destabilized the closed conformation of the lid structure and converted the mutase into a lyase that exhibited up to 44‐fold increased reaction rates in the enantioselective deamination of (R)‐β‐phenylalanine. In addition, the amination rates of cinnamic acid yielding optically pure (S)‐α‐ and (R)‐β‐phenylalanine were doubled. The applicability of the mutant enzyme for kinetic resolution and asymmetric amination could be shown by biocatalysis on a preparative scale.