Abstract
The development of biocatalytic tools for the synthesis of optically pure amines has been the focus of abundant research in recent years. Among other enzymes, imine reductases have attracted much attention associated with the possibility of attaining chiral secondary amines. Furthermore, the reductive aminase activity associated with some of these enzymes has facilitated the production of optically pure amines from a prochiral ketone, a transformation that opens doors to an incredible array of products. In this work, the genomes from native Streptomyces strains isolated in our lab have been explored on the search for novel imine reductases. Application of different structural criteria and sequence motif filters allowed the identification of two novel enzymes, Ss-IRED_S and Ss-IRED_R. While the former presented outstanding activity towards bulky cyclic imine substrates, the latter presented reductive aminase activity with the assayed ketones. A bioinformatic analysis based on modeling and docking studies was performed in order to explain the differences in enzyme activity, searching for additional criteria that could be used to analyze enzyme candidates in silico, providing additional tools for enzyme selection for a particular application. Our findings suggest that imine reductase activity could be predicted by this analysis, overall accounting for the number of docking positions that meet the catalytic requirements.
Highlights
Synthesis of chiral amines is of particular interest for synthetic organic chemistry due to its presence in many biologically active molecules
Due to the convenience of this reaction, which allows the synthesis of secondary amines directly from ketones, efforts have been made to expand the repertoire of enzymes capable of performing reductive amination (Kohls, Steffen-Munsberg, and Höhne 2014; Schrittwieser, Velikogne, and Kroutil 2015; Wetzl et al, 2016; Aleku et al, 2017; Maugeri and Rother 2017; France et al, 2018)
Two new IREDs, Ss-IRED_S and Ss-IRED_R, have been identified from native Streptomyces strains isolated from Uruguayan soil
Summary
Synthesis of chiral amines is of particular interest for synthetic organic chemistry due to its presence in many biologically active molecules. IREDs are NADPH-dependent oxidoreductases able to catalyze the asymmetric reduction of different imines and iminium ions to produce the corresponding secondary and tertiary amines (Cosgrove et al, 2018; Höhne 2019). These enzymes can be found in different biosynthetic pathways. An interesting article published by Turner et al made a characterization of 80 putative and 15 previously described IREDs across 10 different transformations and confirmed that reductive amination catalysis is not limited to any particular subgroup or sequence motif (Montgomery et al, 2020)
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