17 research outputs found
The new alpha-amino acid N-omega-hydroxy-nor-L-arginine: A high-affinity inhibitor of arginase well adapted to bind to its manganese cluster
International audiencexx
Recognition of α-Amino Acids Bearing Various CNOH Functions by Nitric Oxide Synthase and Arginase Involves Very Different Structural Determinants â€
Designing modulators of dimethylarginine dimethylaminohydrolase (DDAH): A focus on selectivity over arginase
Testimony of the Correlation Between the Reactive Histidine Residue and the Arginase Catalytic Mechanism Using a Biochromatographic Concept and Mutagenesis Experiments
Biosynthesis of the putative siderophore erythrochelin requires unprecedented crosstalk between separate nonribosomal peptide gene clusters
The genome of the erythromycin-producing bacterium Saccharopolyspora erythraea contains many orphan secondary metabolite gene clusters including two (nrps3 and nrps5) predicted to govern biosynthesis of nonribosomal peptide-based siderophores. We report here the production by S. erythraea, even under iron-sufficient conditions, of a 2,5-diketopiperazine siderophore candidate we have named erythrochelin. Deletion of the nonribosomal peptide synthetase (NRPS) gene ercD within the nrps5 cluster abolished erythrochelin production. The tetrapeptide backbone of erythrochelin (α-N-acetyl-δ-N-acetyl-δ-N-hydroxyornithine-serine-δ-N-hydroxyornithine-δ-N-acetyl-δ-N-hydroxyornithine) suggests an orthodox colinear model for erythrochelin assembly. Curiously, the δ-N-acetyltransferase required for erythrochelin biosynthesis is encoded within a remote NRPS-cluster (nrps1) whose own NRPS contains an inactivating mutation. Disruption of the nrps1 gene mcd abolished erythrochelin biosynthesis, which could then be restored by addition of synthetic L-δ-N-acetyl-δ-N-hydroxyornithine, confirming an unprecedented example of functional crosstalk between nrps clusters