Conformational Rearrangements Enable Iterative Backbone N-methylation in RiPP Biosynthesis

Overview

Journal Nat Commun

Specialty Biology

Date 2021 Sep 10

PMID 34504067

Citations 20

Authors

Fredarla S Miller

Kathryn K Crone

Matthew R Jensen

Sudipta Shaw

William R Harcombe

Mikael H Elias

Michael F Freeman

Affiliations

Soon will be listed here.

Abstract

Peptide backbone α-N-methylations change the physicochemical properties of amide bonds to provide structural constraints and other favorable characteristics including biological membrane permeability to peptides. Borosin natural product pathways are the only known ribosomally encoded and posttranslationally modified peptides (RiPPs) pathways to incorporate backbone α-N-methylations on translated peptides. Here we report the discovery of type IV borosin natural product pathways (termed 'split borosins'), featuring an iteratively acting α-N-methyltransferase and separate precursor peptide substrate from the metal-respiring bacterium Shewanella oneidensis. A series of enzyme-precursor complexes reveal multiple conformational states for both α-N-methyltransferase and substrate. Along with mutational and kinetic analyses, our results give rare context into potential strategies for iterative maturation of RiPPs.

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