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Because they are a part of numerous molecule-synthesis processes deployed in the pharmaceutical and agrochemical sectors, not to mention in chemistry more generally, amines are in high demand. To meet this latter, novel and sustainable means for synthesizing these organic compounds need to be invented and furthermore need to take into account current environmental issues. Thereto, new biocatalytic solutions are being developed to enable and respond to the needs of greener chemistry. Seeking to contribute to these goals and via the exploration of biodiversity, the biocatalysis team at L2BMS (UMR8030/Genoscope) has identified amine-synthesizing enzymes and shed light on the key catalytic characteristics of a number of them. The results of their work were recently published in Frontiers in Catalysis.
To meet the high demands for amines in the pharmaceutical and agrochemical sectors and the fine and heavy chemicals industries, not only do new and sustainable amine-production processes need to be developed, they also need to take current economic and environmental issues into account. Biocatalysis employs biological enzymes for the production of compounds. It thus stands as a greener alternative to conventional chemistry while also contributing to several of the United Nations' Sustainable Development Goals.
Biocatalysis enables more environmentally-friendly catalytic workflows while providing the benefits of the chemo and stereoselectivity of the enzymes.
The discipline was originally developed around lipases and transaminases. Biocatalytic solutions for amines entered the picture in 2015 with the discovery of enzymes that catalyze reductive amination for carbonyl compounds.
In 2019, in partnership with Genoscope's Bioconversion Activities Screening Platform, the biocatalysis team at L2BMS (UMR8030/Genoscope) discovered native amine dehydrogenases (nat-AmDHs) via the exploration of bacterial biodiversity. Nat-AmDHs catalyze asymmetric reductive amination of ketones using only ammonia (a low-cost source of amine) and a recyclable cofactor, NAD(P)H. They favor (S)-amination, rarely described with other enzyme families catalyzing the same reaction.
in an effort to meet development criteria for biocatalysis in industry, complementary studies are underway to explore the catalytic possibilities of these enzymes and discover novel homologs.
Within this context, L2BMS's biocatalysis team, in partnership with researchers from Delft University, has recently demonstrated a key characteristic of the nat-AmDH family, specifically the ability of some of its enzymes to catalyze ketone reduction, i.e., the reduction of ketones into corresponding alcohols, in the absence of ammonia (KRED).
Structural model studies (done in partnership with Bioinformatics Analyses for Genomics and Metabolism Laboratory /UMR8030/Genoscope) and kinetics analyses provided information suggesting that the ketoreduction is dependent on the reaction's alcohol/amine couple.
This double activity may be advantageous in certain synthesis applications where AmDH and KRED activities could be alternatively activated or deactivated as a function of reaction conditions.
This work by the biocatalysis team and its partners was published in Frontiers in Catalysis.
The exploration of the enzyme family has enabled the identification of new AmDHs with differing characteristics. The team continues their work, still aimed at screening biodiversity in depth and extending the applications of these enzymes in synthetic chemistry.
This work was financed by the MODAMDH (ANR-19-CE07-0007) and ALADIN (ANR-21-ESRE-0021) projects.
Native amine dehydrogenases can catalyze the direct reduction of carbonyl compounds to alcohols in the absence of ammonia | Frontiers in Catalysis
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