Genome mining and characterisation of a novel transaminase with remote stereoselectivity
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Supplementary Information
Date
2019-12-30
Authors
Gavin, Declan P.
Reen, F. Jerry
Rocha-Martin, J.
Abreu-Castilla, I.
Woods, David F.
Foley, Aoife M.
Sanchez-Murcia, P. A.
Schwarz, Maria
O'Neill, P.
Maguire, Anita R.
Journal Title
Journal ISSN
Volume Title
Publisher
Springer Nature Switzerland AG
Published Version
Abstract
Microbial enzymes from pristine niches can potentially deliver disruptive opportunities in synthetic routes to Active Pharmaceutical Ingredients and intermediates in the Pharmaceutical Industry. Advances in green chemistry technologies and the importance of stereochemical control, further underscores the application of enzyme-based solutions in chemical synthesis. The rich tapestry of microbial diversity in the oceanic ecosystem encodes a capacity for novel biotransformations arising from the chemical complexity of this largely unexplored bioactive reservoir. Here we report a novel omega-transaminase discovered in a marine sponge Pseudovibrio sp. isolate. Remote stereoselection using a transaminase has been demonstrated for the first time using this novel protein. Application to the resolution of an intermediate in the synthesis of sertraline highlights the synthetic potential of this novel biocatalyst discovered through genomic mining. Integrated chemico-genomics revealed a unique substrate profile, while molecular modelling provided structural insights into this 'first in class' selectivity at a remote chiral centre.
Description
Keywords
Asymmetric-synthesis , Chiral amines , Mediated resolution , Directed evolution , Kinetic resolution , One-pot , Efficient , Oxidase , Cascade , Protein
Citation
Gavin, Declan P.; Reen, F. Jerry; Rocha-Martin, J.; Abreu-Castilla, I.;Woods, David F.;Foley, Aoife M.;Sanchez-Murcia, P. A.;Schwarz, Maria;O'Neill, P.;Maguire, Anita R.; O'Gara, Fergal (2019) 'Genome mining and characterisation of a novel transaminase with remote stereoselectivity', Scientific Reports, 9, 20285 (15 pp). doi: 10.1038/s41598-019-56612-7