Bioactive C-Glycosides from Bacterial Secondary Metabolism

Abstract

C-Glycosides are commonly regarded as unusual structures, but they are far more prevalent among natural products than is imagined. This review discusses the C-glycosidic compounds produced by various bacteria, particularly the "biosynthetically talented" Streptomyces. The major structure types are presented, along with brief descriptions of the known biological and pharmacological properties of the compounds. Recent work has uncovered the genetic basis for the biosynthesis of several bacterial C-glycosides, and emphasis is placed on those cases where it has been possible to identify (at least provisionally) the C-glycosyltransferase in the pathway. Prospects for biosynthetic engineering, combinatorial biosynthesis, or glycorandomization in C-glycosidic natural products are briefly discussed.

Natural‐Product Sugar Biosynthesis and Enzymatic Glycodiversification

“…[233] Two possible mechanisms for C-GT catalysis have been proposed (Scheme 15 e). [80] One mechanism (path A) involves the initial formation of an O-glycoside and subsequent intramolecular rearrangement to an ortho-C-glycoside.…”

“…Although neither mechanism has been experimentally verified, direct formation of the Cglycosidic linkage is particularly appealing for natural products containing C-glycosyl substituents both ortho and para to the activating phenolate group. [233] Several natural products, such as gilvocarcin and enterobactin, contain only para-C-glycosides, which would be difficult to form with an O-glycosylation/rearrangement sequence. [18,234,235] Recent studies of UrdGT2, a C-GT involved in the biosynthesis of urdamycin in Streptomyces fradiae Tü2717, have provided important insights into the mechanism of C-glycosylation (Scheme 15 f).…”

The Occurrence, Fate and Biological Activities ofC-glycosyl Flavonoids in the Human Diet

“…Flavonoid glycosylation usually proceeds by the attachment of a sugar substituent to a hydroxyl group during in planta flavonoid synthesis, thus conferring Oglycosylation via preservation of the hydroxyl oxygen in the glycosidic linkage. Such a biochemically demanding reaction is assumed to be required in order to stabilise the receiving flavonoid, which subsequently exhibits the function of both the donor and receptor molecules in planta (Hultin, 2005). This synthetic O-glycosylation reaction is catalysed by a myriad of family-1 O-glycosyltransferases (OGTs) in the presence of nucleotide-diphosphosugars (UDP-sugars) as substituent group donors participating in a final step during flavonoid synthesis (Lairson et al, 2008).…”

Structural basis for C-ribosylation in the alnumycin A biosynthetic pathway

“…This mode of attachment is in contrast to the majority of GTs that most often attach carbohydrates through an O-glycosidic bond but that are then susceptible to hydrolysis in the acidic environment of the stomach or by the action of glycosidases in the small intestine (10). The more chemically stable C-glycosylated metabolites (11) are, by comparison, rare and only found in selected natural products (12,13), such as the polyketide antibiotic urdamycin (14).…”