Chemoenzymatic synthesis of diverse thiohydroximates from glucosinolate-utilizing enzymes from Helix pomatia and Caldicellulosiruptor saccharolyticus.
Thiohydroximates comprise a diverse class of compounds important in both biological and industrial chemistry. Their syntheses are generally limited to simple alkyl and aryl compounds with few stereocenters and a narrow range of functional groups. We hypothesized that sequential action of two recombinant enzymes, a sulfatase from Helix pomatia and a β-O-glucosidase from Caldicellulosiruptor saccharolyticus, on glucosinolates would allow synthesis of thiohydroximates from a structurally broad array of abundant precursors. We report successful synthesis of thiohydroximates of varied chemical classes, including from homochiral compounds of demonstrated biological activity. The chemoenzymatic synthetic route reported here should allow access to many, if not all, of the thiohydroximate core structures of the ~200 known naturally occurring glucosinolates. The enrichment of this group for compounds with possible pharmacological potential is discussed.
Department of Molecular Signal Processing, Leibniz Institute for Plant Biochemistry, 06120 Halle (Saale), Germany.
Jakub
J
Kopycki
Jürgen
J
Schmidt
Steffen
S
Abel
C
C
Douglas Grubb
D000818:Animals; D049851:Gastropoda / Q000201:enzymology* / Q000235:genetics; D005959:Glucosidases / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D005961:Glucosinolates / Q000378:metabolism*; D006094:Gram-Positive Bacteria / Q000201:enzymology* / Q000235:genetics; D010091:Oximes / Q000378:metabolism*; D011994:Recombinant Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism; D013429:Sulfatases / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*
D005961:Glucosinolates; D010091:Oximes; D011994:Recombinant Proteins; C010519:thiohydroximic acid ester; D013429:Sulfatases; D005959:Glucosidases