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Enzyme discovery for use in the manufacture of chemicals, requiring high stereoselectivities, continues to be an important avenue of research. Here, a sequence directed metagenomics approach is described to identify short chain carbonyl reductases. PCR from a metagenomic template generated 37 enzymes, with an average 25% sequence identity, twelve of which showed interesting activities in initial screens. Six of the most productive enzymes were then tested against a panel of 21 substrates, including bulkier substrates that have been noted as challenging in biocatalytic reductions. Two enzymes were selected for further studies with the Wieland Miescher ketone. Notably, enzyme SDR‐17, when co‐expressed with a co‐factor recycling system produced the anti‐(4aR,5S) isomer in excellent isolated yields of 89% and 99% e.e. These results demonstrate the viability of a sequence directed metagenomics approach for the identification of multiple homologous sequences with low similarity, that can yield highly stereoselective enzymes with applicability in industrial biocatalysis. [ABSTRACT FROM AUTHOR]

Methyltransferases are gaining traction as a method to achieve greener and regioselective methylations of a wide array of substrates. In this work, a halide methyltransferase biomethylation cascade was successfully adapted with the incorporation of a methionine adenosyltransferase to generate the S‐adenosyl‐L‐methionine (SAM) methylation cofactor in situ from less costly ATP and L‐methionine, instead of directly adding SAM to start the cascade. Furthermore, this cascade was applied to achieve novel catechol and tetrahydroisoquinoline methylations with the O‐methyltransferases RnCOMT, MxSafC and NpN4OMT with high conversions and regioselectivities. In addition, the cascade was successfully trialled with the less toxic methyl group donor, methyl tosylate. [ABSTRACT FROM AUTHOR]