Smart ATP regeneration system for chemoenzymatic amide bond formation - Archive ouverte HAL Accéder directement au contenu
Poster De Conférence Année : 2019

Smart ATP regeneration system for chemoenzymatic amide bond formation

Résumé

The amide function is widespread in many natural and synthetic compounds such as pharma-ceuticals and polymers. Amide bond formation is therefore a very important chemical reaction in chemical industries, especially pharmaceutical, and many efforts have been devoted to develop efficient synthetic methods.[1] Regardless the approach, by conventional chemistry or biocatalysis, the acylation of amines with activated carboxylic acid derivatives is the most common method to access to the amide function.[2] In our project, we focused on thermophilic CoA ligases which catalyze the formation of an activated carboxylic acid as thioester via an adenylate intermediate in presence of Adenosine TriPhosphate (ATP) and coenzyme A.[3] When the reaction is carried out at high temperature, we were able to form amide bond from the adenylate intermediate by amine nucleophilic attack to reach 96% conversion in 24h. To reduce the reaction cost, an ATP regeneration system has been implemented. A thermophilic polyphosphate kinase 2 Class III allows ATP regeneration from AMP and polyphosphate. In addition, to eliminate pyrophosphate inhibition, a thermophilic inorganic pyrophosphatase is necessary for the recycling system to catalyze the hydrolysis of pyrophosphate into inorganic phosphate. This presentation describes the reaction catalyzed by the CoA ligase with the ATP regeneration. References: 1. Roughley, S.D. and A.M. Jordan, (2011) The Medicinal Chemist’s Toolbox: An Analysis of Reactions Used in the Pursuit of Drug Candidates. J Med Chem, 54(10): p. 3451-3479. 2. Dunetz, J.R., J. Magano, and G.A. Weisenburger, (2016) Large-Scale Applications of Amide Coupling Reagents for the Synthesis of Pharmaceuticals. Org. Process Res. Dev., 20(2): p. 140-177. 3. Gulick, A.M., (2009) Conformational Dynamics in the Acyl-CoA Synthetases, Adenylation Domains of Non-ribosomal Peptide Synthetases, and Firefly Luciferase. ACS Chemical Biology, 4(10): p. 811-827.
Fichier non déposé

Dates et versions

hal-04354478 , version 1 (19-12-2023)

Identifiants

  • HAL Id : hal-04354478 , version 1

Citer

Chloé M. Lelièvre, Mélanie Balandras, Adrien Debard, Virginie Pellouin, Jean-Louis Petit, et al.. Smart ATP regeneration system for chemoenzymatic amide bond formation. 14th Biotrans symposium, Jul 2019, Groningen, Netherlands. ⟨hal-04354478⟩
13 Consultations
0 Téléchargements

Partager

Gmail Facebook X LinkedIn More