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PMID: 17220414 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Sequencing and analysis of the biosynthetic gene cluster of the lipopeptide antibiotic Friulimicin in Actinoplanes friuliensis.

Antimicrobial agents and chemotherapy ·Vol. 51 ·No. 3 ·2007-03-00 ·Pages 1028-37

Müller C, Nolden S, Gebhardt P, Heinzelmann E, Lange C, Puk O, Welzel K, Wohlleben W, Schwartz D

Abstract

Actinoplanes friuliensis produces the lipopeptide antibiotic friulimicin, which is a cyclic peptide with one exocyclic amino acid linked to a branched-chain fatty acid acyl residue. The structural relationship to daptomycin and the excellent antibacterial performance of friulimicin make the antibiotic an attractive drug candidate. The complete friulimicin biosynthetic gene cluster of 24 open reading frames from A. friuliensis was sequenced and analyzed. In addition to genes for regulation, self-resistance, and transport, the cluster contains genes encoding peptide synthetases, proteins involved in the synthesis and linkage of the fatty acid component of the antibiotic, and proteins involved in the synthesis of the nonproteinogenic amino acids pipecolinic acid, methylaspartic acid, and 2,3-diaminobutyric acid. By using heterologous gene expression in Escherichia coli, we provide biochemical evidence for the stereoselective synthesis of L-pipecolinic acid by the deduced protein of the lysine cyclodeaminase gene pip. Furthermore, we show the involvement of the dabA and dabB genes in the biosynthesis of 2,3-diaminobutyric acid by gene inactivation and subsequent feeding experiments.

MeSH Terms
Aminobutyrates/metabolism Anti-Bacterial Agents/biosynthesis Blotting, Southern Chromatography, High Pressure Liquid Chromatography, Thin Layer Conjugation, Genetic DNA, Bacterial/genetics,metabolism Electrophoresis, Polyacrylamide Gel Escherichia coli/metabolism Genetic Complementation Test In Situ Hybridization Microbial Sensitivity Tests Micromonosporaceae/genetics,metabolism Molecular Sequence Data Multigene Family Mutation/genetics,physiology Pipecolic Acids/metabolism Plasmids/genetics
Chemicals
Aminobutyrates Anti-Bacterial Agents DNA, Bacterial Pipecolic Acids 2,4-diaminobutyric acid pipecolic acid
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Müller C
Leibniz-Institut für Naturstoff-Forschung und Infektionsbiologie e.ZV., Hans-Knöll-Institut, Beutenbergstrasse 11, 07745 Jena, Germany.
Nolden S
Gebhardt P
Heinzelmann E
Lange C
Puk O
Welzel K
Wohlleben W
Schwartz D
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Article Info
Journal
Antimicrobial agents and chemotherapy
Abbr.
Antimicrob Agents Chemother
ISSN
0066-4804
DOI
10.1128/AAC.00942-06
Published
2007-03-00
Epub
2007-00-12
Pages
1028-37
Language
English
Region
United States
NLM ID
0315061
PMCID
PMC1803135
Subset
IM
Databases
GENBANK
AJ488769
External Links
PubMed source DOI: 10.1128/AAC.00942-06 PMC Full Text View journal details
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