Reprogramming biocatalytic futile cycles through computational engineering of stereochemical promiscuity to create an amine racemase.

ABSTRACT: Repurposing the intrinsic properties of natural enzymes can offer a viable solution to current synthetic challenges through the development of novel biocatalytic processes. Although amino acid racemases are ubiquitous in living organisms, an amine racemase (AR) has not yet been discovered despite its synthetic potential for producing chiral amines. Here, we report the creation of an AR based on the serendipitous discovery that amine transaminases (ATAs) can perform stereoinversion of 2-aminobutane. Kinetic modeling revealed that the unexpected off-pathway activity results from stereochemically promiscuous futile cycles due to incomplete stereoselectivity for 2-aminobutane. This finding motivated us to engineer an S-selective ATA through in silico alanine scanning and empirical combinatoria

SUBMITTER: Han SW 

PROVIDER: S-EPMC10761954 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature