In conclusion, we have engineered a highly selective aminotransferase for the synthesis of a key chiral intermediate of the anti-HIV drug Lenacapavir 1. The sterically demanding nature of the ketone substrate necessitated adoption of a 'substrate walk' approach to unlock desired activity starting from a parent template with no observable activity for the target transformation. Efforts are now ongoing to further engineer this enzyme into an industrial biocatalyst for the large-scale manufacture of Lenacapavir 1.