Secondary metabolites: Glucosinolates

Biosynthesis (S-glycosyltransferase): synthesis & biodegradation (S-glycosidase)

 

Sulfur atom is one of the most flexible atoms regarding its chemistry and Sulfur in Nature is a key element in living cells. One of the main research streams in our group is dedicated to sulfur containing plant secondary metabolites which are quite uncommon in nature. Among them, Glucosinolates (GLs) are naturally occurring thiosugars mainly found in the botanical order Brassicales. They represent a unique family of more than 130 different molecules: their structural framework invariably results from a combination of three parts: a β-D-glucopyranosyl unit, a unique O-sulfated anomeric thiohydroximate function and a broad library of aglycons, whose structure varies in the vegetal kingdom depending on the species (over 130 different aglycons). Their biological and ecological roles are remarkable due to an original mechanism of plant defense against insects, bacteria or fungus. This mechanism is very well known as the “mustard oil bomb”. Myrosinase (thioglucoside glucohydrolase EC 3.2.3.1) is responsible for the revelation of this property through the hydrolysis of the thioglycosidic bond which liberates strong electrophiles. Myrosinase is the only enzyme able to hydrolyse those unusual thiosaccharidic compounds and one of the few enzymes able to hydrolyse a thioglycosidic bond. Biosynthesis of GLs is unique and unusual in Nature, where a glucosyltransferase elaborates an anomeric S-glycosidic bond (collaboration with Prof R. Daniellou within ICOA).

Différents challenges et sujets liés aux glucosinolates sont actuellement étudiés au sein de notre équipe :

 

Different topics and challenges related to glucosinolates are studied in our research group:

  • development of innovative methods of synthesis of this intriguing thio-function, an O-sulfated thiohydroximate linked to the anomeric position of D-glucopyranose;
  • understanding their original biosynthesis unique in Nature, where a specific S-glucosyltransferase (S-UGT) is able to form the C-S anomeric bond. We are developing the synthesis of substrates and inhibitors of S-UGT to understand the mechanism underlying the selectivity of this C-S bond formation;
  • understanding the mode of action and interaction of myrosinase, a specific glucohydrolase able to hydrolyse the C-S anomeric bond;
  • study of the hydrolysis by-products (ITCs, OZTs ...):
    • as useful partners for some original thiochemistry,
    • as bioconjugation partners for the development of novel ligation tools and (3) for their biological applications as chemopreventive agents with antiangiogenic properties for example.

 

Multidisciplinary program supported by : Extrasynthèse, La Ligue Contre le Cancer.