The use of NCBs makes CFB more industrially feasible due to their reduced cost compared to the natural nicotinamide cofactors. However, many NCBs tested to date are also at risk of decomposing at the nicotinamide moiety in buffers used in CFB. The proposed mechanism of nicotinamide decomposition by Alivisatos et al. is through addition across the 5,6-double bond in the 1,4-dihydropyridine ring, depicted in Scheme S1. This decomposition occurs most quickly in a potassium phosphate buffer, which often yields high enzyme activity. To further promote the applicability of NCBs in CFB, we propose their stability should be included as a feature to optimize during engineering campaigns.