Precise control over the chemoselectivity of the electron transfer events is required for the proposed reaction. Reduction of the nitroalkanes is thermodynamically favored by comparison to all but the most electronically activated alkyl halides (nitroalkanes Ep/2 = ~ -0.9 V vs. saturated calomel electrode, SCE ; alkyl halides Ep/2 = -1.1 V to -2.5 V vs. SCE 25 ). To achieve the desired reaction, we require a catalyst that will preferentially reduce alkyl halides instead of the nitroalkanes. We recently demonstrated that flavin-dependent 'ene'-reductases (EREDs) can reduce alkyl halides using protein templated charge-transfer (CT) complexes. Protein templated complexes provide the opportunity for substrate binding to override the inherent thermodynamic preference in electron transfer events. If the protein only forms the CT complex with the alkyl halide, it would be selectively reduced over the nitroalkane. Finally, EREDs can precisely control the radical terminating HAT step, enabling the formation of products with high levels of enantioselectivity. We initiated our studies by exploring the photoenzymatic coupling of α-chloroamide 1a (Ep/2 = -1.65 V vs. SCE) with 1-nitroethylbenzene 2a (Ep/2 = -0.89 V vs. SCE) catalyzed by a panel of EREDs under cyan light irradiation (λmax = 497 nm) (Supplementary Table ). To our delight, many of the enzymes provided the desired cross-coupled product 3a, with none providing the nitrated product (Supplementary Table ). The most promising catalyst was the 'ene'-reductase from Caulobacter segnis (CsER), providing product 3a with moderate yield (28%) but excellent enantioselectivity (95:5 er). We hypothesized that the modest yield is likely due to inadequate concentration of the nitronate at pH 8.0 (nitroalkane/nitronate = 200:1, pKa of 2a is 10.3) . Indeed, in moving to the more basic reaction conditions at pH 9.0 (nitroalkane/nitronate = 20:1), the desired product is formed in high yield and excellent enantioselectivity (92% yield, 95:5 er) for the (S)-enantiomer, outperforming other tested EREDs (Fig. and Supplementary Table ). The ERED variant from Gluconobacter (GluER-T36A) favors the formation of the (R)-enantiomer of the product (51% yield, 90:10 er), providing a complimentary catalyst for accessing both enantiomers of the product (Fig. ). Control experiments confirmed that ERED, cyan light, and NADPH regeneration system (GDH/NADP + /glucose) are crucial for the desired reactivity (Supplementary Table ). Notably, this reaction can be run on a preparative scale and afford product 3a in 72% isolated yield with no changes in enantioselectivity. We solved the crystal structure of wild-type CsER, and the docking model of 3a with CsER suggests the (S)-preference of CsER in this reaction (Supplementary Fig. ). Notably, the coupled product is not formed when the same reaction is attempted using photoredox catalysts. Instead, we observed nitroalkane reduction to the oxime, highlighting that this reactivity is unique to biocatalysis. accepted as XEC partners with α-chloroamide 1a. α-Aryl nitroethanes possessing electrondonating or electron-withdrawing substituents at the meta-and para-position were efficiently converted to the desired enantioenriched β-stereogenic amide products (9-16) in yields of 80-98% with excellent enantioselectivity (>95:5 er). Ortho-substituted α-aryl nitroalkanes were less tolerated in the reaction, only the ortho-fluoro substituted nitroalkane was accepted to provide product 8 in 28% yield and 94:6 er (Fig. , and Supplementary Fig. ). In addition, the larger substrate α-naphthalenyl nitroethane was well tolerated in this reaction, providing the corresponding product 17 with 58% yield and excellent enantioselectivity (99:1 er). This enzyme, however, was limited to relatively small alkyl substituents at the α-position. While the ethyl group was well accepted (19, 64% yield and 98:2 er), larger groups, such as n-propyl, were poorly reactive. Pleasingly, CsER could also accommodate heterocycles, including the electron-rich αthiophene and the electron-deficient α-pyridine nitroethanes, providing the respective βheterocycle substituted chiral amide products (22-24) in 40-95% yield and high enantioselectivity (up to 99:1 er). The compatibility of this photoenzyme was further highlighted by the acceptance of α-nitroester as a coupling partner, giving β-stereogenic 1,4-dicarbonyl product 25 in 96% yield and 82:18 er (Fig. ).