The current trend in Chemistry is to perform the energy transition successfully by considering cheaper and greener alternatives. This can be achieved by the substitution of some chemical steps by biocatalyzed ones or the design of new enzymatic routes, thus reducing waste and polluting organometallic catalysts.
As useful building blocks in chemists’ toolbox, chiral amines are also present in more than 40% of Active Pharmaceuticals Ingredients (API). To access the necessary high enantiomeric purity, various unsustainable multi-step processes are required. Green alternative routes to obtain this highly widespread function is so still one of the main challenge for the (pharmaceutical) industry.
For 5 years, the Laboratory of Organic Chemistry and Biocatalysis (LCOB, UMR Genomic Metabolic, CEA-Genoscope) has been working on the one-step asymmetric reductive amination of ketones performed by specific enzymes, termed Amine Dehydrogenases (AmDHs), in presence of free ammonia. Recently, they found the first native AmDHs by a pairwise sequence alignment-based strategy thus, for the first time, succeeded in identifying genes encoding for them.
Being part of the collaborative MODAMDH project of LCOB, the LABGeM aims to widen the search area to the microbial biodiversity, gathered in all publicly-available and Genoscope’s (meta)-genomic databases, in order to discover new AmDHs with different features (substrate scope, selectivity, stability, structures). This will be undertaken by applying both sequence-driven and 3D-guided approaches, taking distant homologies into account.
Keywords: Biocatalysis, Amine Dehydrogenases, Metagenomic, Biodiversity.
References:
- Mayol et al. 2019, DOI: 10.1038/s41929-019-0249-z
- Mayol et al. 2016, DOI: 10.1039/C6CY01625A
- Bastard et al. 2013, DOI: 10.1038/nchembio.1387