ja9b05151_si_001.pdf (2.96 MB)
Download fileAliphatic Ether Bond Formation Expands the Scope of Radical SAM Enzymes in Natural Product Biosynthesis
journal contribution
posted on 18.06.2019, 00:00 authored by Kenzie
A. Clark, Leah B. Bushin, Mohammad R. SeyedsayamdostThe 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.