The ornithine cyclodeaminase/µ-crystallin superfamily of proteins: A novel family of oxidoreductases for the biocatalytic synthesis of chiral amines

Biocatalysis, one of the most ecologically friendly methods for synthesising chiral synthons, has emerged as a desirable process for manufacturing active pharmaceutical ingredients and agrochemicals, most of which contain one or more chiral amine moieties. Compared with the traditional biocatalytic processes for the synthesis of chiral amines involving lipases or transaminases, enzymatic imine reduction is a more promising approach. The single-step enzymatic reduction of prochiral imines to the corresponding amines can yield 100% of the required enantiomer without any by-products. Furthermore, the reduction of imines generated in situ through the condensation of amines and carbonyl compounds can be used to synthesise almost any primary, secondary, or tertiary amine. In the past decade, several imine-reducing enzyme families, such as Streptomyces imine reductases (IReds), native amine dehydrogenases and engineered leucine/phenylalanine dehydrogenases and opine dehydrogenases, have been explored. The ornithine cyclodeaminase/µ-crystallin (OCD/CRYM) superfamily consists of proteins capable of imine reduction, which have been relatively unexplored regarding the synthesis of chiral amines. The proteins in this family are ubiquitously distributed in all three domains of life and catalyse diverse and unique reactions. This review is aimed at summarising current knowledge on this superfamily and exploring its potential in biocatalysis. After a brief discussion of their discovery, the known members of the OCD/CRYM superfamily are broadly classified on the basis of the reactions that they catalyse, and their biochemical characteristics and biological roles are described in detail. This is followed by a discussion of the overall structure, active sites and proposed reaction mechanisms, with common themes drawn among members. Finally, the applications of these enzymes, particularly in the synthesis of various chiral synthons, are summarised.