Gui_2023_Nat.Chem.Biol__

Reference

Title : Cofactorless oxygenases guide anthraquinone-fused enediyne biosynthesis - Gui_2023_Nat.Chem.Biol__
Author(s) : Gui C , Kalkreuter E , Liu YC , Li G , Steele AD , Yang D , Chang C , Shen B
Ref : Nat Chemical Biology , : , 2023
Abstract :

The anthraquinone-fused enediynes (AFEs) combine an anthraquinone moiety and a ten-membered enediyne core capable of generating a cytotoxic diradical species. AFE cyclization is triggered by opening the F-ring epoxide, which is also the site of the most structural diversity. Previous studies of tiancimycin A, a heavily modified AFE, have revealed a cryptic aldehyde blocking installation of the epoxide, and no unassigned oxidases could be predicted within the tnm biosynthetic gene cluster. Here we identify two consecutively acting cofactorless oxygenases derived from methyltransferase and alpha/beta-hydrolase protein folds, TnmJ and TnmK2, respectively, that are responsible for F-ring tailoring in tiancimycin biosynthesis by comparative genomics. Further biochemical and structural characterizations reveal that the electron-rich AFE anthraquinone moiety assists in catalyzing deformylation, epoxidation and oxidative ring cleavage without exogenous cofactors. These enzymes therefore fill important knowledge gaps for the biosynthesis of this class of molecules and the underappreciated family of cofactorless oxygenases.

PubMedSearch : Gui_2023_Nat.Chem.Biol__
PubMedID: 37945897
Gene_locus related to this paper: strsp-TnmK2

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Citations formats

Gui C, Kalkreuter E, Liu YC, Li G, Steele AD, Yang D, Chang C, Shen B (2023)
Cofactorless oxygenases guide anthraquinone-fused enediyne biosynthesis
Nat Chemical Biology :

Gui C, Kalkreuter E, Liu YC, Li G, Steele AD, Yang D, Chang C, Shen B (2023)
Nat Chemical Biology :