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bioRxiv · 10.1101/338681

Catalytic Use of a Leader Peptide in the Biosynthesis of 3-Thiaglutamate

van der Donk, W.·Funk, M. A.·Ting, C.
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Abstract

Small molecule natural products are key modulators of many types of intra- and interspecies communication. The availability of genome sequences allows the discovery of pathways to previously unknown natural products. We describe here a pathway in which a ribosomally synthesized small peptide serves as a catalytic scaffold on which a small-molecule anti-metabolite is biosynthesized in Pseudomonas syringae. First, a cysteine residue is transferred from Cys-tRNA to the C-terminus of the peptide, a reaction that replaces ribosomal protein synthesis. Then, a translocation of the cysteine thiol from the {beta}-carbon to the -carbon is catalyzed by an oxidase that removes the {beta}-carbon as formate. The resulting thiol is carboxymethylated and proteolysis releases 3-thiaglutamate, in the process regenerating the peptide scaffold. This pathway features three previously unknown biochemical processes.

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van der Donk, W., Funk, M. A., Ting, C.. 2018-06-04. Catalytic Use of a Leader Peptide in the Biosynthesis of 3-Thiaglutamate. https://doi.org/10.1101/338681

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