Visible-light-driven pyridoxal radical biocatalysis offers a promising approach for developing stereoselective intermolecular radical reactions that have no known precedent in biology or chemistry. Now, building on the engineering of pyridoxal-dependent carboligases, a multienzyme photobiocatalytic cascade enables the stereoselective synthesis of polysubstituted unnatural prolines, including 2,5-anti-stereoisomers that remain challenging to access by other methods.