Initially, a panel of potential diol substrates was subjected to activity screening (see Supporting Information). Alongside previously tested aliphatic diols, diethylene glycol and N-methyl-diethanolamine were screened to investigate whether the methodology may be applied to form morpholines Scheme 1. Potential biocatalytic routes for AcCo6 AdRedam catalysed amine diol annulation. Reaction conditions: 10 mM alcohol, 100 mM amine, 0.1 mM NADP + , 80 mM glucose, 1 mg mL -1 AdRedAm, 1 mg mL -1 AcCO6, 0.5 mg mL -1 TaGDH, 0.5 mg mL -1 CBL*, 50 mg mL and piperazines. While diethylene glycol and N-methyl-diethanolamine were moderately active substrates for the engineered and wild-type choline oxidases respectively, applying them under imine reductase cascade conditions suggested no product formation by GC-MS analysis. Despite this, correct masses for heterocyclic products were successfully detected from the panel of aliphatic diols (Table ). While the formation of saturated heterocycles was observed for 6-8 membered rings, 1,4-butanediol (9) largely yielded products of mass consistent with pyrroles, possibly through a Paal-Knorr reaction. Incubating 9 with a primary amine and lone AcCO 6 did not yield a possible pyrrole product, indicating an involvement of the IRED in this transformation. Both N-methylpyrrole (9iii) and N-methylpiperidine (3iii) were undetected by GC-MS, but we speculate this is due to co-retention with the solvent due to low boiling point. While the majority of products were observed as single peaks in GC chromatograms, no reaction conversions are claimed due to the potential for undetectable side reactions such as enzyme cross-coupling.