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SHR Neuro Cancer Cardio Lipid Metab Microb

Bitter, J; Pfeiffer, M; Borg, AJE; Kuhlmann, K; Pavkov-Keller, T; Sánchez-Murcia, PA; Nidetzky, B.
Enzymatic β-elimination in natural product O- and C-glycoside deglycosylation.
Nat Commun. 2023; 14(1): 7123 Doi: 10.1038/s41467-023-42750-0 [OPEN ACCESS]
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Co-authors Med Uni Graz: Sánchez Murcia Pedro Alejandro
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Abstract:: Biological degradation of natural product glycosides involves, alongside hydrolysis, β-elimination for glycosidic bond cleavage. Here, we discover an O-glycoside β-eliminase (OGE) from Agrobacterium tumefaciens that converts the C3-oxidized O-β-D-glucoside of phloretin (a plant-derived flavonoid) into the aglycone and the 2-hydroxy-3-keto-glycal elimination product. While unrelated in sequence, OGE is structurally homologous to, and shows effectively the same Mn²⁺ active site as, the C-glycoside deglycosylating enzyme (CGE) from a human intestinal bacterium implicated in β-elimination of 3-keto C-β-D-glucosides. We show that CGE catalyzes β-elimination of 3-keto O- and C-β-D-glucosides while OGE is specific for the O-glycoside substrate. Substrate comparisons and mutagenesis for CGE uncover positioning of aglycone for protonic assistance by the enzyme as critically important for C-glycoside cleavage. Collectively, our study suggests convergent evolution of active site for β-elimination of 3-keto O-β-D-glucosides. C-Glycoside cleavage is a specialized feature of this active site which is elicited by substrate through finely tuned enzyme-aglycone interactions.
Find related publications in this database (using NLM MeSH Indexing): Humans - administration & dosage; Glycosides - chemistry; Flavonoids - metabolism; Glucosides - metabolism; Intestines - microbiology; Cardiac Glycosides - administration & dosage; Substrate Specificity - administration & dosage