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CoA-ligases
- PI: Anne Zaparucha
CoA ligases (EC 6.2.1.X) are ATP-dependent enzymes that catalyze the adenylation of carboxylic acids followed by conversion of the acyl-adenylate into the corresponding coenzyme A thioester. This native reaction can be diverted by adding an external nucleophile, such as an amine, to the acyl-adenylate, leading to formation of the corresponding amide. The non-catalyzed addition of the external nucleophile is favored at elevated temperature.
To implement a one-pot chemoenzymatic cascade, thermophilic CoA ligases are required so that they can withstand the temperature of the reaction medium. We therefore built a collection of thermophilic CoA ligases. In parallel, we developed an ATP recycling system based on the combined action of a PPK2-III polyphosphate kinase and a pyrophosphatase.
After exploring the synthesis of unsubstituted lactams, a topic that led to a collaboration with D.B. Janssen and A.-M. Thunnissen (University of Groningen, Netherlands), we are now working on the synthesis of functionalized lactams.
This research theme is continuing through the ANR SMALA project, which we coordinate (ANR-21-CE07-0061).