| N-acylation during glidobactin biosynthesis by the tridomain nonribosomal peptide synthetase module GlbF. | |
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MedLine Citation:
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PMID: 21035730 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Glidobactins are hybrid NRPS-PKS natural products that function as irreversible proteasome inhibitors. A variety of medium chain 2(E),4(E)-diene fatty acids N-acylate the peptidolactam core and contribute significantly to the potency of proteasome inhibition. We have expressed the initiation NRPS module GlbF (C-A-T) in Escherichia coli and observe soluble active protein only on coexpression with the 8 kDa MbtH-like protein, GlbE. Following adenylation and installation of Thr as a T-domain thioester, the starter condensation domain utilizes fatty acyl-CoA donors to acylate the Thr(1) amino group and generate the fatty acyl-Thr(1)-S-pantetheinyl-GlbF intermediate to be used in subsequent chain elongation. Previously proposed to be mediated via acyl carrier protein fatty acid donors, direct utilization of fatty acyl-CoA donors for N-acylation of T-domain tethered amino acids is likely a common strategy for chain initiation in NRPS-mediated lipopeptide biosynthesis. |
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Authors:
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Heidi J Imker; Daniel Krahn; Jérôme Clerc; Markus Kaiser; Christopher T Walsh |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Chemistry & biology Volume: 17 ISSN: 1879-1301 ISO Abbreviation: Chem. Biol. Publication Date: 2010 Oct |
Date Detail:
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Created Date: 2010-11-01 Completed Date: 2011-02-22 Revised Date: 2011-10-31 |
Medline Journal Info:
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Nlm Unique ID: 9500160 Medline TA: Chem Biol Country: United States |
Other Details:
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Languages: eng Pagination: 1077-83 Citation Subset: IM |
Copyright Information:
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Copyright © 2010 Elsevier Ltd. All rights reserved. |
Affiliation:
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Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, 240 Longwood Avenue, Boston, MA 02115, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Acyl Coenzyme A
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chemistry,
metabolism Acylation Bacterial Proteins / genetics, metabolism* Burkholderia / enzymology Peptide Synthases / chemistry, genetics, metabolism* Peptides, Cyclic / biosynthesis Protein Structure, Tertiary |
| Grant Support | |
ID/Acronym/Agency:
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GM49338/GM/NIGMS NIH HHS; R01 GM049338-18/GM/NIGMS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Acyl Coenzyme A; 0/Bacterial Proteins; 0/Peptides, Cyclic; 108351-50-4/glidobactin A; EC 6.3.2.-/Peptide Synthases; EC 6.3.2.-/non-ribosomal peptide synthase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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