Lewis acid catalysis is a powerful tool in organic synthesis. However, biocatalytic Lewis acid catalysis has been limited in its reaction scope and diversity, constraining its synthetic utility. In this study, we expand the scope of biocatalytic Lewis acid catalysis by integrating abiotic ene reactions into metalloenzymatic catalysis. We found that substituting the iron centre with copper enabled SadA, a non-haem iron hydroxylase from Burkholderia ambifaria, to catalyse abiotic Conia-ene reactions. A high-throughput screening platform based on fluorogenic click chemistry was developed to optimize this abiotic transformation. Using this platform, directed evolution was used to generate variants that produced a range of Conia-ene cyclization products with stereogenic quaternary carbon centres, achieving up to 99% yield, 250 total turnovers and 99% enantiomeric excess. Mechanistic studies suggested that the reaction proceeded through a dual activation mechanism, where the Cu(II) centre activated both the ketoester and alkyne moieties.