Cogan_2020_ACS.Chem.Biol_15_2783

Reference

Title : Structural Basis for Enzymatic Off-Loading of Hybrid Polyketides by Dieckmann Condensation - Cogan_2020_ACS.Chem.Biol_15_2783
Author(s) : Cogan DP , Ly J , Nair SK
Ref : ACS Chemical Biology , 15 :2783 , 2020
Abstract :

While several bioactive natural products that contain tetramate or pyridone heterocycles have been described, information on the enzymology underpinning these functionalities has been limited. Here we biochemically characterize an off-loading Dieckmann cyclase, NcmC, that installs the tetramate headgroup in nocamycin, a hybrid polyketide/nonribosomal peptide natural product. Crystal structures of the enzyme (1.6 A) and its covalent complex with the epoxide cerulenin (1.6 A) guide additional structure-based mutagenesis and product-profile analyses. Our results offer mechanistic insights into how the conserved thioesterase-like scaffold has been adapted to perform a new chemical reaction, namely, heterocyclization. Additional bioinformatics combined with docking and modeling identifies likely candidates for heterocycle formation in underexplored gene clusters and uncovers a modular basis of substrate recognition by the two subdomains of these Dieckmann cyclases.

PubMedSearch : Cogan_2020_ACS.Chem.Biol_15_2783
PubMedID: 33017142
Gene_locus related to this paper: 9pseu-NcmC

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Citations formats

Cogan DP, Ly J, Nair SK (2020)
Structural Basis for Enzymatic Off-Loading of Hybrid Polyketides by Dieckmann Condensation
ACS Chemical Biology 15 :2783

Cogan DP, Ly J, Nair SK (2020)
ACS Chemical Biology 15 :2783