RT Journal Article
T1 Genome mining and characterisation of a novel transaminase with remote stereoselectivity
A1 Gavin, Declan
A1 Reen, Jerry
A1 Rocha Martín, Javier
A1 Abreu-Castilla, Ignacio
A1 Woods, David
A1 Foley, Aoife
A1 Sánchez-Murcia, Pedro
A1 Schwarz, Maria
A1 O’Neill, Pat
A1 Maguire, Anita
A1 O’Gara, Fergal
AB 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 ω-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.
PB Springer Nature
SN 2045-2322
YR 2019
FD 2019
LK https://hdl.handle.net/20.500.14352/94110
UL https://hdl.handle.net/20.500.14352/94110
LA eng
NO Gavin, D.P., Reen, F.J., Rocha-Martin, J. et al. Genome mining and characterisation of a novel transaminase with remote stereoselectivity. Sci Rep 9, 20285 (2019). https://doi.org/10.1038/s41598-019-56612-7
NO FundingEsta investigación fue financiada en parte por financiación de Enterprise Ireland (CF-2017-0757-P; IP-2015-0390), el Health Research Board (HRB-ILP-POR-2019-004), el Health Research Board/Irish Thoracic Sociedad (MRCG-2018-16; MRCG-2014-6), Comisión Europea (EU2020-634486-2015), Science Foundation Ireland (SSPC-3, 12/RC/2275_2; SSPC-2, 12/RC/2275; 15/TIDA/2977; SFI09/RFP/BMT2350), el Consejo Irlandés de Investigación en Ciencia, Ingeniería y Tecnología (GOIPG/2014/647), Fundación de Fibrosis Quística, EE. UU. (OG1710). PAS-M. agradece al FWF austriaco (Proyecto M 2260) por su apoyo financiero.
NO Enterprise Ireland
NO Health Research Board (Ireland)
NO Irish Toracic Society
NO European Commission
NO Science Foundation Ireland
NO Irish Research Council for Science, Engineering and Technology
NO Cystic Fibrosis Foundation (USA)
NO Austrian Science Fund
DS Docta Complutense
RD 4 abr 2025