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Applied and Environmental Microbiology, May 2008, p. 3085-3093, Vol. 74, No. 10
0099-2240/08/$08.00+0     doi:10.1128/AEM.02848-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Isolation and Identification of Rhizoxin Analogs from Pseudomonas fluorescens Pf-5 by Using a Genomic Mining Strategy{triangledown} ,{dagger}

Joyce E. Loper,1 Marcella D. Henkels,1 Brenda T. Shaffer,1 Frederick A. Valeriote,2 and Harald Gross3*

Horticultural Crops Research Laboratory, Agricultural Research Service, United States Department of Agriculture, Corvallis, Oregon 97330,1 Henry Ford Health System, Detroit, Michigan 48202,2 Institute for Pharmaceutical Biology, University of Bonn, 53115 Bonn, Germany3

Received 18 December 2007/ Accepted 10 March 2008

The products synthesized from a hybrid polyketide synthase/nonribosomal peptide synthetase gene cluster in the genome of Pseudomonas fluorescens Pf-5 were identified using a genomics-guided strategy involving insertional mutagenesis and subsequent metabolite profiling. Five analogs of rhizoxin, a 16-member macrolide with antifungal, phytotoxic, and antitumor activities, were produced by Pf-5, but not by a mutant with an insertion in the gene cluster. The five rhizoxin analogs, one of which had not been described previously, were differentially toxic to two agriculturally important plant pathogens, Botrytis cinerea and Phytophthora ramorum. The rhizoxin analogs also caused swelling of rice roots, a symptom characteristic of rhizoxin itself, but were less toxic to pea and cucumber roots. Of the rhizoxin analogs produced by Pf-5, the predominant compound, WF-1360 F, and the newly described compound 22Z-WF-1360 F were most toxic against the two plant pathogens and three plant species. These rhizoxin analogs were tested against a panel of human cancer lines, and they exhibited potent but nonselective cytotoxicity. This study highlights the value of the genomic sequence of the soil bacterium P. fluorescens Pf-5 in providing leads for the discovery of novel metabolites with significant biological properties.

* Corresponding author. Mailing address: Institute for Pharmaceutical Biology, University of Bonn, Nussallee 6, 53115 Bonn, Germany. Phone: 49 228 73-2676. Fax: 49 228 73-3250. E-mail: harald.gross{at}uni-bonn.de

{triangledown} Published ahead of print on 14 March 2008.

{dagger} Supplemental material for this article may be found at http://aem.asm.org/.

Applied and Environmental Microbiology, May 2008, p. 3085-3093, Vol. 74, No. 10
0099-2240/08/$08.00+0     doi:10.1128/AEM.02848-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.





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