Imine Reductases, Reductive Aminases, and Amine Oxidases for the Synthesis of Chiral Amines: Discovery, Characterization, and Synthetic Applications

• Published in: Methods in enzymology Vol. 608; p. 131
• Main Authors: Cosgrove, Sebastian C, Brzezniak, Agata, France, Scott P, Ramsden, Jeremy I, Mangas-Sanchez, Juan, Montgomery, Sarah L, Heath, Rachel S, Turner, Nicholas J
• Format: Journal Article
• Language: English
• Published: United States 2018
• Subjects: Amines - chemistry; Amines - metabolism; Aminohydrolases - genetics; Aminohydrolases - metabolism; Aspergillus niger - enzymology; Aspergillus niger - genetics; Aspergillus niger - metabolism; Bacteria - enzymology; Bacteria - genetics; Bacteria - metabolism; Biocatalysis; Escherichia coli - enzymology; Escherichia coli - genetics; Escherichia coli - metabolism; Fungi - enzymology; Fungi - genetics; Fungi - metabolism; Imines - chemistry; Imines - metabolism; Monoamine Oxidase - genetics; Monoamine Oxidase - metabolism; Oxidation-Reduction; Oxidoreductases - genetics; Oxidoreductases - metabolism; Protein Engineering - methods; Stereoisomerism; Streptomyces - enzymology; Streptomyces - genetics; Streptomyces - metabolism; Synthetic Biology - methods; Imine reductase; In vivo and in vitro cascade reactions; Amine oxidase library screening; Reductive aminase; Amine oxidase; Biotransformations
• DOI: 10.1016/bs.mie.2018.04.022

Synthesis of the chiral amine moiety is a key challenge for synthetic organic chemistry due to its prevalence in many biologically active molecules. Imine reductase and amine oxidase enzymes have enabled the biocatalytic synthesis of a host of chiral amine compounds. In this chapter, procedures for the synthesis of chiral amines using imine reductases (IREDs), the recently discovered IRED homologues reductive aminases, and amine oxidases (AOs) are described. Amine oxidases have been the subject of mutagenesis approaches for improvement of substrate scope. The high-throughput screening method for determining active variants in amine oxidase libraries is illustrated. Finally, in an approach which takes inspiration from nature, many enzymes can be combined with each other in cascade reactions. The incorporation of imine reductase and monoamine oxidase biocatalysts into several cascade reactions, both in vitro and in vivo (where the approach moves toward synthetic biology), is reported.