Title : A Hydrolase-Catalyzed Cyclization Forms the Fused Bicyclic beta-Lactone in Vibralactone - Feng_2020_Angew.Chem.Int.Ed.Engl_59_7209 |
Author(s) : Feng KN , Yang YL , Xu YX , Zhang Y , Feng T , Huang SX , Liu JK , Zeng Y |
Ref : Angew Chem Int Ed Engl , 59 :7209 , 2020 |
Abstract :
Vibralactone is isolated from the basidiomycete fungus Boreostereum vibrans as one of the strongest lipase inhibitors. Its unusual beta-lactone-fused bicycle is derived from an aryl ring moiety via an oxidative ring-expansion prior to an intramolecular cyclization. Here, we report the discovery of the cyclase VibC which belongs to the alpha/beta-hydrolase superfamily and is involved in the vibralactone biosynthesis. Biochemical and crystal studies suggest that VibC may catalyze an aldol or an electrocyclic reaction initiated by the catalytic Ser-His-Asp triad. For the aldol and pericyclic chemistry in living cells, VibC is a unique hydrolase performing the carbocycle formation of an oxepinone to a fused bicyclic b-lactone. This presents a naturally occurring new enzyme reaction in both aldol and hydrolase (bio)chemistry that will guide future exploitation of these enzymes in synthetic biology for chemical diversity expansion of natural products. |
PubMedSearch : Feng_2020_Angew.Chem.Int.Ed.Engl_59_7209 |
PubMedID: 32050043 |
Gene_locus related to this paper: 9agam-VibC , stehr-Sh.112560 |
Inhibitor | Vibralactone |
Substrate | 1,5-Seco-vibralactone |
Gene_locus | 9agam-VibC stehr-Sh.112560 |
Structure | 6KD0 |
Feng KN, Yang YL, Xu YX, Zhang Y, Feng T, Huang SX, Liu JK, Zeng Y (2020)
A Hydrolase-Catalyzed Cyclization Forms the Fused Bicyclic beta-Lactone in Vibralactone
Angew Chem Int Ed Engl
59 :7209
Feng KN, Yang YL, Xu YX, Zhang Y, Feng T, Huang SX, Liu JK, Zeng Y (2020)
Angew Chem Int Ed Engl
59 :7209