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Aromatic electron-deficient heterocycles, such as pyridines, are found in many biologically relevant structures, including those with medicinal applications. Methods for their substitution can streamline the synthesis of valuable molecules and allow access to unexplored chemical space. However, enantioselective methods for these derivatizations remain lacking, especially at remote stereocenters. Here, we present a photoenzymatic reaction for the reductive coupling of electron-deficient heterocycles with alkenes using flavin-dependent “ene”-reductases. This transformation results in the generation of a γ-stereocenter with high enantioselectivity. We propose that this light-driven transformation proceeds via excitation of a transient enzyme–substrate complex, enabling the enzyme to access the reductive potential needed for radical initiation when the substrates are bound in the active site. This work represents a stereoselective method for synthesizing derivatives of pyridine and similar heterocycles and an expansion of the substrate capabilities of “ene”-reductases in chemical synthesis.