Artículo
Extended substrate range of thiamine diphosphate-dependent MenD enzyme by coupling of two C–C-bonding reactions
Schapfl, Matthias; Baier, Shiromi; Fries, Alexander Erich
; Ferlaino, Sascha; Waltzer, Simon; Müller, Michael; Sprenger, Georg A.
Fecha de publicación:
10/2018
Editorial:
Springer
Revista:
Applied Microbiology and Biotechnology
ISSN:
0175-7598
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
Carboligations catalyzed by aldolases or thiamine diphosphate (ThDP)-dependent enzymes are well-known in biocatalysis to deliver enantioselective chain elongation reactions. A pyruvate-dependent aldolase (2-oxo-3-deoxy-6-phosphogluconate aldolase [EDA]) introduces a chiral center when reacting with the electrophile, glyoxylic acid, delivering the (S)-enantiomer of (4S)-4-hydroxy-2-oxoglutarate [(S)-HOG]. The ThDP-dependent enzyme MenD (2-succinyl-5-enol-pyruvyl-6-hydroxy-3-cyclohexene-1-carboxylate synthase (SEPHCHC synthase)) enables access to highly functionalized substances by forming intermolecular C?C bonds with Michael acceptor compounds by a Stetter-like 1,4- or a benzoin-condensation 1,2-addition of activated succinyl semialdehyde (ThDP adduct formed by decarboxylation of 2-oxoglutarate). MenD-catalyzed reactions are characterized by high chemo- and regioselectivity. Here, we report (S)-HOG, in situ formed by EDA, to serve as new donor substrate for MenD in 1,4-addition reactions with 2,3-trans-CHD (2,3-trans-dihydroxy-cyclohexadiene carboxylate) and acrylic acid. Likewise, (S)-HOG serves as donor in 1,2-additions with aromatic (benzaldehyde) and aliphatic (hexanal) aldehydes. This enzyme cascade of two subsequent C?C bond formations (EDA aldolase and a ThDP-dependent carboligase, MenD) generates two new stereocenters.
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Articulos(INCITAP)
Articulos de INST.D/CS D/L/TIERRA Y AMBIENTALES D/L/PAMPA
Articulos de INST.D/CS D/L/TIERRA Y AMBIENTALES D/L/PAMPA
Citación
Schapfl, Matthias; Baier, Shiromi; Fries, Alexander Erich; Ferlaino, Sascha; Waltzer, Simon; et al.; Extended substrate range of thiamine diphosphate-dependent MenD enzyme by coupling of two C–C-bonding reactions; Springer; Applied Microbiology and Biotechnology; 102; 19; 10-2018; 8359-8372
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