Transaminases for industrial biocatalysis: novel enzyme discovery

Abstract

Transaminases (TAms) are important enzymes for the production of chiral amines for the pharmaceutical and fine chemical industries. Novel TAms for use in these industries have been discovered using a range of approaches, including activity-guided methods and homologous sequence searches from cultured microorganisms to searches using key motifs and metagenomic mining of environmental DNA libraries. This mini-review focuses on the methods used for TAm discovery over the past two decades, analyzing the changing trends in the field and highlighting the advantages and drawbacks of the respective approaches used. This review will also discuss the role of protein engineering in the development of novel TAms and explore possible directions for future TAm discovery for application in industrial biocatalysis. KEY POINTS: • The past two decades of TAm enzyme discovery approaches are explored. • TAm sequences are phylogenetically analyzed and compared to other discovery methods. • Benefits and drawbacks of discovery approaches for novel biocatalysts are discussed. • The role of protein engineering and future discovery directions is highlighted.

Keywords: Biocatalysis; Chiral amine; Enzyme discovery; Metagenomics; Transaminase.

Fig. 1

Cumulative number of reported TAms, grouped by discovery approach from 1997 to 2019

Fig. 2

Phylogenetic tree highlighting evolutionary relationships between characterized TAms, categorized by method of discovery and enantiopreference. A neighbor-joining tree was produced using MEGA v. 7.0.26 with bootstrap values of 1000, following protein sequence alignment by ClustalW

Fig. 3

Comparison of the numbers of reported R- and S-selective TAms by discovery method from 1997 to 2019