Monoamine Oxidase: Tunable Activity for Amine Resolution and Functionalization

Abstract

Monoamine oxidases (MAO) are biocatalysts for the oxidation of a wide range of different amines including α-chiral amines. Their high selectivity and activity, along with the environmental advantages inherent to enzymatic synthesis, place MAOs in the spotlight for future application in industrial biocatalytic processes. To date, these enzymes have been used in both amine resolution and amine functionalization. MAO from Micrococcus luteus was employed in the multienzymatic synthesis of benzylisoquinoline alkaloids, and MAO from Aspergillus niger (MAO-N) was used in deracemization experiments. MAO-N was also applied to several biobio and biochemo cascades for amine functionalization, exploring the increased reactivity of the imine/iminium species. MAO-N has been extensively engineered to alter the size and electronic properties of its active site, creating variants capable of oxidizing a broad range of α-aliphatic and aromatic amines. This Review provides an in-depth analysis of current research in the biocatalytic applications of MAOs, coupled with available data on the limitations and challenges that still hinder their industrial application. It also highlights the importance of chiral amines and the biochemical importance of human MAO in metabolism. Finally, the development of alternative amine oxidases, such as CHAO or HLNO/HDNO, is briefly surveyed, along with a discussion on possible future developments on this field.

Is it time for biocatalysis in fragment-based drug discovery?

“…catalyse reductive amination. 44,45 This gives rise to biocatalytic strategies for the synthesis of asymmetric azepanes, a biologically relevant yet underrepresented class of heterocycle. Despite enantiocomplementary methods that proceed with full selectivity, the reaction itself is a simple reduction that may only generate products with a singular substitution at the a carbon.…”

Kinetic Resolution of Racemic Amines to Enantiopure (S)-amines by a Biocatalytic Cascade Employing Amine Dehydrogenase and Alanine Dehydrogenase

“…A surge of interest has occurred in recent years in the use of superior biocatalytic alternatives to the chemical syntheses of chiral amines [13,14]. Enzymes such as transaminases [15], imine reductases [16], amine oxidases [17], P450 monooxygenases [18], lipases [19], and berberine bridge enzyme [20] have been successfully employed for chiral amines synthesis. More recently, amine dehydrogenases (AmDHs)-catalyzing the reductive amination of ketones using ammonia and generating only water racemic amines for the synthesis of their enantiopure (S)-amine counterparts.…”

A Visible‐Light Promoted Amine Oxidation Catalyzed by a Cp*Ir Complex

“…Hence, MAOs have been engineered to improve their substrate scope, selectivity, and stability for industrial purposes. [1] To complement enzymes, organometallic catalysts have been developed for the dehydrogenation of N-heterocycles. [2,3] To drive the oxidation of amines to completion, most organometallic catalysts require a sacrificial hydrogen acceptor, an undesirable feature from an atom-economical perspective.…”