We began our investigations by screening an in-house panel of NRs (BaNTR1 from Bacillus amyloliquefaciens, NfsA from Escherichia coli, BmoNR from Bacillus mojavensis, and BpNR from Blautia producta) using 2-nitrobenzylamine (1a) as a substrate . In the first experiment using BaNTR1, it was found that within one hour substrate 1a was mostly depleted. At the same time, none of the potential products 2a, 3a, and 4a could be identified with gas chromatography-mass spectrometry (GC-MS) analysis. Instead, 1Hindazole (6a') was detected (Figure and 2B right, Figure ). The same was found for NfsA and BmoNR, while BpNR was not active towards 1a (Figure left, Figure ). 2Hindazole (6a), which is formed according to the proposed mechanism, was not detected due to its quick tautomerization to the more stable 1H-form 6a' . Control experiments confirmed that the reaction proceeded solely in the presence of BaNTR1, NfsA and BmoNR. The total turnover number (TON = molesproduct ×molesNR -1 ) of BaNTR1, NfsA and BmoNR was determined to be around 240, aligning well with the generally high catalytic activity of NRs . The two most active enzymes, BaNTR1 and NfsA, were used for all subsequent experiments. At the same time, BaNTR1 and NfsA were used as representatives of NADH-dependent and NADPH-dependent NRs, respectively, ensuring that an enzyme with a suitable cofactor preference was available for subsequent cascade development with other oxidoreductases. No NR 6