Genome mining and characterisation of a novel transaminase with remote stereoselectivity
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 underscore...
| Autores: | , , , , , , , , , , |
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| Tipo de documento: | artigo |
| Data de publicação: | 2019 |
| País: | España |
| Recursos: | Universidad Complutense de Madrid (UCM) |
| Repositório: | Docta Complutense |
| Idioma: | inglês |
| OAI Identifier: | oai:docta.ucm.es:20.500.14352/94110 |
| Acesso em linha: | https://hdl.handle.net/20.500.14352/94110 |
| Access Level: | Acceso aberto |
| Palavra-chave: | 577.1 577.2 Bioquímica (Química) Biología molecular (Química) 2302 Bioquímica 2403 Bioquímica 2415 Biología Molecular |
| Resumo: | 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. |
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