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 (alpha-N-acetyl-delta-N-acetyl-delta-N-hydroxyornithine-serine-delta-N-hydroxyornithine-delta-N-acetyl-delta-N-hydroxyornithine) suggests an orthodox colinear model for erythrochelin assembly. Curiously, the delta-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-delta-N-acetyl-delta-N-hydroxyornithine, confirming an unprecedented example of functional crosstalk between nrps clusters.
Lazos
Orestis
O
Department of Biochemistry, University of Cambridge, Cambridge CB2 1GA, UK.
Tosin
Manuela
M
Slusarczyk
Adrian L
AL
Boakes
Steven
S
Cortés
Jesus
J
Sidebottom
Philip J
PJ
Leadlay
Peter F
PF
D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000096:biosynthesis* / Q000737:chemistry / Q000494:pharmacology; D019295:Computational Biology; D054659:Diketopiperazines / Q000737:chemistry / Q000494:pharmacology; D005798:Genes, Bacterial; D008969:Molecular Sequence Data; D005810:Multigene Family; D009842:Oligopeptides / Q000096:biosynthesis* / Q000737:chemistry / Q000494:pharmacology; D046908:Peptide Biosynthesis, Nucleic Acid-Independent / Q000235:genetics*; D010453:Peptide Synthases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D017262:Siderophores / Q000096:biosynthesis* / Q000737:chemistry / Q000494:pharmacology
D000900:Anti-Bacterial Agents; D054659:Diketopiperazines; D009842:Oligopeptides; D017262:Siderophores; C549789:erythrochelin; D010453:Peptide Synthases; C104385:non-ribosomal peptide synthase