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 HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Bruheim, P.
Right arrow Articles by Zotchev, S. B.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Bruheim, P.
Right arrow Articles by Zotchev, S. B.

 Previous Article  |  Next Article 

Antimicrobial Agents and Chemotherapy, November 2004, p. 4120-4129, Vol. 48, No. 11
0066-4804/04/$08.00+0     DOI: 10.1128/AAC.48.11.4120-4129.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Chemical Diversity of Polyene Macrolides Produced by Streptomyces noursei ATCC 11455 and Recombinant Strain ERD44 with Genetically Altered Polyketide Synthase NysC

Per Bruheim,1 Sven E.F. Borgos,1 Pascale Tsan,2 Håvard Sletta,3 Trond E. Ellingsen,3 Jean-Marc Lancelin,2 and Sergey B. Zotchev1*

Department of Biotechnology, Norwegian University of Science and Technology,1 Department of Industrial Biotechnology, SINTEF Materials and Chemistry, SINTEF, Trondheim, Norway,3 RMN Biomoléculaire, Unité Mixte de Recherche, Université Claude Bernard-Lyon 1, CNRS Sciences Analytiques, ESCPE-Lyon, Villeurbanne, France2

Received 28 January 2004/ Returned for modification 29 March 2004/ Accepted 11 July 2004

The gram-positive bacterium Streptomyces noursei ATCC 11455 produces a complex mixture of polyene macrolides generally termed nystatins. Although the structures for nystatins A1 and A3 have been reported, the identities of other components of the nystatin complex remain obscure. Analyses of the culture extract from the S. noursei wild type revealed the presence of several nystatin-related compounds for which chemical structures could be suggested on the basis of their molecular weights, their UV spectra, and knowledge of the nystatin biosynthetic pathway. Nuclear magnetic resonance (NMR) studies with one of these polyene macrolides identified it as a nystatin analogue containing a mycarose moiety at C-35. A similar investigation was performed with the culture extract of the ERD44 mutant, which has a genetically altered polyketide synthase (PKS) NysC and which was previously shown to produce a heptaene nystatin analogue. The latter compound, tentatively named S44HP, and its derivative, which contains two deoxysugar moieties, were purified; and their structures were confirmed by NMR analysis. Nystatin analogues with an expanded macrolactone ring were also observed in the extract of the ERD44 mutant, suggesting that the altered PKS can "stutter" during the polyketide chain assembly. These data provide new insights into the biosynthesis of polyene macrolide antibiotics and the functionalities of PKSs and post-PKS modification enzymes.

* Corresponding author. Mailing address: Department of Biotechnology, Norwegian University of Science and Technology, N-7491 Trondheim, Norway. Phone: 47 73 59 86 79. Fax: 47 73 59 12 83. E-mail: sergey.zotchev{at}biotech.ntnu.no.

Antimicrobial Agents and Chemotherapy, November 2004, p. 4120-4129, Vol. 48, No. 11
0066-4804/04/$08.00+0     DOI: 10.1128/AAC.48.11.4120-4129.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Nedal, A., Sletta, H., Brautaset, T., Borgos, S. E. F., Sekurova, O. N., Ellingsen, T. E., Zotchev, S. B. (2007). Analysis of the Mycosamine Biosynthesis and Attachment Genes in the Nystatin Biosynthetic Gene Cluster of Streptomyces noursei ATCC 11455. Appl. Environ. Microbiol. 73: 7400-7407 [Abstract] [Full Text]  
  • Volokhan, O., Sletta, H., Ellingsen, T. E., Zotchev, S. B. (2006). Characterization of the P450 Monooxygenase NysL, Responsible for C-10 Hydroxylation during Biosynthesis of the Polyene Macrolide Antibiotic Nystatin in Streptomyces noursei. Appl. Environ. Microbiol. 72: 2514-2519 [Abstract] [Full Text]  
  • Sletta, H., Borgos, S. E. F., Bruheim, P., Sekurova, O. N., Grasdalen, H., Aune, R., Ellingsen, T. E., Zotchev, S. B. (2005). Nystatin Biosynthesis and Transport: nysH and nysG Genes Encoding a Putative ABC Transporter System in Streptomyces noursei ATCC 11455 Are Required for Efficient Conversion of 10-Deoxynystatin to Nystatin. Antimicrob. Agents Chemother. 49: 4576-4583 [Abstract] [Full Text]  
  • Razonable, R. R., Henault, M., Watson, H. L., Paya, C. V. (2005). Nystatin Induces Secretion of Interleukin (IL)-1{beta}, IL-8, and Tumor Necrosis Factor Alpha by a Toll-Like Receptor-Dependent Mechanism. Antimicrob. Agents Chemother. 49: 3546-3549 [Abstract] [Full Text]  


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