The Nonribosomal Peptide Synthetase Enzyme DdaD Tethers Nβ-Fumaramoyl-l-2,3-diaminopropionate for Fe(II)/α-Ketoglutarate-Dependent Epoxidation by DdaC during Dapdiamide Antibiotic Biosynthesis
- 14 October 2010
- journal article
- research article
- Published by American Chemical Society (ACS) in Journal of the American Chemical Society
- Vol. 132 (44), 15773-15781
- https://doi.org/10.1021/ja1072367
Abstract
The gene cluster from Pantoea agglomerans responsible for biosynthesis of the dapdiamide antibiotics encodes an adenylation−thiolation didomain protein, DdaD, and an Fe(II)/α-ketoglutarate-dependent dioxygenase homologue, DdaC. Here we show that DdaD, a nonribosomal peptide synthetase module, activates and sequesters Nβ-fumaramoyl-l-2,3-diaminopropionate as a covalently tethered thioester for subsequent oxidative modification of the fumaramoyl group. DdaC catalyzes Fe(II)- and α-ketoglutarate-dependent epoxidation of the covalently bound Nβ-fumaramoyl-l-2,3-diaminopropionyl-S-DdaD species to generate Nβ-epoxysuccinamoyl-DAP (DAP = 2,3-diaminopropionate) in thioester linkage to DdaD. After hydrolytic release, Nβ-epoxysuccinamoyl-DAP can be ligated to l-valine by the ATP-dependent ligase DdaF to form the natural antibiotic Nβ-epoxysuccinamoyl-DAP-Val.Keywords
This publication has 38 references indexed in Scilit:
- Dapdiamides, Tripeptide Antibiotics Formed by Unconventional Amide LigasesJournal of Natural Products, 2009
- The ATP-Dependent Amide Ligases DdaG and DdaF Assemble the Fumaramoyl-Dipeptide Scaffold of the Dapdiamide AntibioticsBiochemistry, 2009
- Stereospecific Synthesis of threo- and erythro-β-Hydroxyglutamic Acid During Kutzneride BiosynthesisJournal of the American Chemical Society, 2009
- Accessing natural product biosynthetic processes by mass spectrometryCurrent Opinion in Chemical Biology, 2008
- β-Hydroxylation of the Aspartyl Residue in the Phytotoxin Syringomycin E: Characterization of Two Candidate Hydroxylases AspH and SyrP in Pseudomonas syringaeBiochemistry, 2008
- Mass spectrometry for proteomicsCurrent Opinion in Chemical Biology, 2008
- Facile Detection of Acyl and Peptidyl Intermediates on Thiotemplate Carrier Domains via Phosphopantetheinyl Elimination Reactions during Tandem Mass SpectrometryBiochemistry, 2006
- Assembly-Line Enzymology for Polyketide and Nonribosomal Peptide Antibiotics: Logic, Machinery, and MechanismsChemical Reviews, 2006
- Fe(II)/α-Ketoglutarate-Dependent Hydroxylases and Related EnzymesCritical Reviews in Biochemistry and Molecular Biology, 2004
- A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye bindingAnalytical Biochemistry, 1976