Expanding the reaction space of aldolases using hydroxypyruvate as a nucleophilic substrate

Véronique de Berardinis (1) , Christine Guérard-Hélaine (2) , Ekaterina Darii (3, 1) , Karine Bastard (3, 4) , Virgil Hélaine (2) , Aline Mariage (3, 1) , Jean-Louis Petit (1) , Nicolas Poupard (2) , Israel Sánchez-Moreno (2) , Mark Stam (3) , Thierry Gefflaut (2) , Marcel Salanoubat (3, 1) , Marielle Lemaire (2)

1 LGBM - Laboratoire de Génomique et Biochimie du Métabolisme
2 ICCF - Institut de Chimie de Clermont-Ferrand
3 UMR 8030 - Génomique métabolique
4 LABGeM - Analyse Bio-Informatique pour la Génomique et le Métabolisme

Aldolases are key biocatalysts for stereoselective C–C bond formation allowing access to polyoxygenated chiral units through direct, efficient, and sustainable synthetic processes. The aldol reaction involving unprotected hydroxypyruvate and an aldehyde offers access to valuable polyhydroxy-α-keto acids. However, this undescribed aldolisation is highly challenging, especially regarding stereoselectivity. This reaction was explored using, as biocatalysts, a collection of aldolases selected from biodiversity. Several enzymes that belong to the same pyruvate aldolase Pfam family (PF03328) were found to produce the desired hexulosonic acids from hydroxypyruvate and D-glyceraldehyde with complementary stereoselectivities. One of them was selected for the proof of concept as a biocatalytic tool to prepare five (3S,4S) aldol adducts through an eco-friendly process.

Domaines: Chimie

Véronique de Berardinis, Christine Guérard-Hélaine, Ekaterina Darii, Karine Bastard, Virgil Hélaine, et al.. Expanding the reaction space of aldolases using hydroxypyruvate as a nucleophilic substrate . Green Chemistry, 2017, 19, pp.519-526. ⟨10.1039/C6GC02652D⟩. ⟨hal-01540868⟩