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Biosynthesis of the putative siderophore erythrochelin requires unprecedented crosstalk between separate nonribosomal peptide gene clusters
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Lazos, Orestis, Tosin, Manuela, Slusarczyk, Adrian L., Boakes, Steven, Cortés, Jesus, Sidebottom, Philip J. and Leadlay, Peter F.. (2010) Biosynthesis of the putative siderophore erythrochelin requires unprecedented crosstalk between separate nonribosomal peptide gene clusters. Chemistry & Biology, Vol.17 (No.2). pp. 160-173. ISSN 1074-5521
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Official URL: http://dx.doi.org/10.1016/j.chembiol.2010.01.011
Abstract
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.
| Item Type: | Journal Article |
|---|---|
| Subjects: | Q Science > QD Chemistry Q Science > QP Physiology Q Science > QR Microbiology |
| Divisions: | Faculty of Science > Chemistry |
| Library of Congress Subject Headings (LCSH): | Siderophores, Biosynthesis, Actinobacteria |
| Journal or Publication Title: | Chemistry & Biology |
| Publisher: | Cell Press |
| ISSN: | 1074-5521 |
| Date: | 2010 |
| Volume: | Vol.17 |
| Number: | No.2 |
| Page Range: | pp. 160-173 |
| Identification Number: | 10.1016/j.chembiol.2010.01.011 |
| Status: | Peer Reviewed |
| Publication Status: | Published |
| Funder: | Nuffield Foundation, Biotechnology and Biological Sciences Research Council (Great Britain) (BBSRC), GlaxoSmithKline |
| Grant number: | 8/CFB17699 (BBSRC) |
| URI: | http://wrap.warwick.ac.uk/id/eprint/40354 |
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