|Title||Aliphatic Ether Bond Formation Expands the Scope of Radical SAM Enzymes in Natural Product Biosynthesis.|
|Publication Type||Journal Article|
|Year of Publication||2019|
|Authors||Clark, KA, Bushin, LB, Seyedsayamdost, MR|
|Journal||J Am Chem Soc|
|Date Published||2019 Jun 27|
The biosynthetic pathways of microbial natural products provide a rich source of novel enzyme-catalyzed transformations. Using a new bioinformatic search strategy, we recently identified an abundance of gene clusters for ribosomally synthesized and post-translationally modified peptides (RiPPs) that contain at least one radical S-adenosylmethionine (RaS) metalloenzyme and are regulated by quorum sensing. In the present study, we characterize a RaS enzyme from one such RiPP gene cluster and find that it installs an aliphatic ether cross-link at an unactivated carbon center, linking the oxygen of a Thr side chain to the α-carbon of a Gln residue. This reaction marks the first ether cross-link installed by a RaS enzyme. Additionally, it leads to a new heterocyclization motif and underlines the utility of our bioinformatics approach in finding new families of RiPP modifications.
|Alternate Journal||J. Am. Chem. Soc.|