Lab discovers new pathway for antimicrobialpeptides princeton J_A_C_S NatureChemistry
The combination of next-generation DNA sequencing technologies and bioinformatics has revitalized natural product discovery. Using a bioinformatic search strategy, we recently identified600 gene clusters in otherwise overlooked streptococci that code for ribosomal peptide natural products synthesized by radical-adenosylmethionine enzymes. These grouped into 16 subfamilies and pointed to an unexplored microbiome biosynthetic landscape.
Here we report the structure, biosynthesis and function of one of these natural product groups, which we term enteropeptins, from the gut microbe. We show three reactions in the biosynthesis of enteropeptins that are each catalysed by a different family of metalloenzymes. Among these, we characterize the founding member of a widespread superfamily of Fe–S-containing methyltransferases, which, together with an Mn-methylornithine in the peptide sequence.
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