This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Müller, C.
Right arrow Articles by Schwartz, D.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Müller, C.
Right arrow Articles by Schwartz, D.

 Previous Article  |  Next Article 

Antimicrobial Agents and Chemotherapy, March 2007, p. 1028-1037, Vol. 51, No. 3
0066-4804/07/$08.00+0     doi:10.1128/AAC.00942-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Sequencing and Analysis of the Biosynthetic Gene Cluster of the Lipopeptide Antibiotic Friulimicin in Actinoplanes friuliensis{triangledown}

C. Müller,1 S. Nolden,1 P. Gebhardt,1 E. Heinzelmann,2 C. Lange,1 O. Puk,4 K. Welzel,3 W. Wohlleben,2 and D. Schwartz1,5*

Leibniz-Institut für Naturstoff-Forschung und Infektionsbiologie e.V., Hans-Knöll-Institut (HKI), Beutenbergstrasse 11, 07745 Jena, Germany,1 Fakultät Biologie, Mikrobiologisches Institut, Mikrobiologie/Biotechnologie, Eberhard-Karls-Universität Tübingen, Auf der Morgenstelle 28, 72076 Tübingen, Germany,2 Combinature Biopharm AG, Robert-Roessle-Strasse 10, 13125 Berlin, Germany,3 GSF-Forschungszentrum für Umwelt und Gesundheit GmbH, Ingolstädter Landstrasse 1, 85764 Neuherberg, Germany,4 Hochschule Esslingen, Kanalstrasse 33, 73728 Esslingen, Germany5

Received 30 July 2006/ Returned for modification 18 October 2006/ Accepted 21 December 2006

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.

* Corresponding author. Mailing address: Hochschule Esslingen, Kanalstrasse 33, 73728 Esslingen, Germany. Phone: 497113973513. Fax: 497113973533. E-mail: schwartz{at}hs-esslingen.de.

{triangledown} Published ahead of print on 12 January 2007.

Antimicrobial Agents and Chemotherapy, March 2007, p. 1028-1037, Vol. 51, No. 3
0066-4804/07/$08.00+0     doi:10.1128/AAC.00942-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.





Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»