Investigation of Amide Bond Formation during Dehydrophos Biosynthesis

Emily C. Ulrich, Despina J. Bougioukou, Wilfred A. Van Der Donk

Research output: Contribution to journalArticle

Abstract

Dehydrophos is a tripeptide phosphonate antibiotic produced by Streptomyces luridus. Its biosynthetic pathway involves the use of aminoacyl-tRNA (aa-tRNA) for amide bond formation. The first amide bond during biosynthesis is formed by DhpH-C, a peptidyltransferase that utilizes Leu-tRNA Leu . DhpH-C is a member of a burgeoning family of natural product biosynthetic enzymes that make use of aa-tRNA outside of canonical translation activities in the cell. Here, we used site-directed mutagenesis of both DhpH-C and tRNA Leu to investigate the enzyme mechanism and substrate specificity, respectively, and analyzed the substrate scope for the production of a set of dipeptides. DhpH-C appears to recognize both the amino acyl group on the tRNA and the tRNA acceptor stem, and the enzyme can accept other hydrophobic residues, in addition to leucine. These results contribute to a better understanding of enzyme-aa-tRNA interactions and the growing exploration of aa-tRNA usage beyond translation.

Original languageEnglish (US)
Pages (from-to)537-541
Number of pages5
JournalACS chemical biology
Volume13
Issue number3
DOIs
StatePublished - Mar 16 2018

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine

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