A new antitumor complex, WF-1360, WF-1360A, B, C, D, E and F.

Kiyoto, Sumio; Kawai, Yoshio; Kawakita, Takashi; King, Eiko; Okuhara, Masakuni; Uchida, Isamu; Tanaka, Hirokazu; Hashimoto, Masashi; Terano, Hiroshi; Kohsaka, Masanobu; Aoki, Hatsuo; Imanaka, Hiroshi

doi:10.7164/antibiotics.39.762

Cited by 56 publications

(48 citation statements)

References 1 publication

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“…Comparison of the metabolite profiles of Pf-5 and an rzxB mutant, derived by allelic-exchange mutagenesis, indicated that the orphan gene cluster was involved in the biosynthesis of at least two compounds with [MϩH] ϩ peaks at 580.7 and 610.3 m/z, respectively (see the supplemental material). From the detected molecular masses and UV spectra, the compounds could be readily dereplicated by a database search as the rhizoxin analogs WF-1360 C and WF-1360 F (25).…”

Section: Resultsmentioning

confidence: 99%

Isolation and Identification of Rhizoxin Analogs from Pseudomonas fluorescens Pf-5 by Using a Genomic Mining Strategy

Loper

Henkels

Shaffer

et al. 2008

Appl Environ Microbiol

113

101

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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.Secondary-metabolite production is a striking characteristic of Pseudomonas spp. (5, 28), and the current availability of genomic sequence data for several Pseudomonas spp. further highlights the capacity for secondary-metabolite production in this group of bacteria. For example, at least 6% of the genome of Pseudomonas fluorescens Pf-5, a rhizosphere bacterium that suppresses plant diseases, is devoted to secondary metabolism, with gene clusters for the biosynthesis of two siderophores, hydrogen cyanide, and several antibiotics (pyrrolnitrin, 2,4-diacetylphloroglucinol, and pyoluteorin) distributed throughout the genome (30). In addition to the secondary metabolites known to be produced by Pf-5 prior to genomic sequencing, three orphan gene clusters were identified in the genome of this bacterium (41). These three orphan genetic loci contain sequences that are characteristic of polyketide synthases (PKS) or nonribosomal peptide synthetases (NRPS) (51). One of the orphan metabolites has since been identified as orfamide A, the founder of a new group of bioactive cyclic lipopeptides that lyses zoospores of an oomycete plant pathogen and functions in the swarming motility of Pf-5 (11). In our continuing effort to identify the products of orphan pathways from the P. fluorescens Pf-5 genome, we describe here the products of a cluster containing genes with characteristic sequences of both PKS and NRPS. Using a screening strategy comparing Pf-5 to a derivative with a mutation in this cluster (12), we isolated and identified several metabolites structurally related to rhizoxin (Fig.

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Section: Resultsmentioning

confidence: 99%

Isolation and Identification of Rhizoxin Analogs from Pseudomonas fluorescens Pf-5 by Using a Genomic Mining Strategy

Loper

Henkels

Shaffer

et al. 2008

Appl Environ Microbiol

113

101

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“…We demonstrated that these metabolites are produced by Pseudomonas strains associated with S. latissima. DAPG, MAPG, PLT and rhizoxins are thus proposed to be chemical mediators of antibacterial, antifungal, cytotoxic and antiprotozoal effects for possible protection of the alga, as shown for terrestrial pseudomonad-host plant associations (Iwasaki et al 1984, Kiyoto et al 1986, de Souza et al 2003, Isnansetyo et al 2003, Jousset et al 2006. Both DAPG and PLT produced by the Pseudomonas strains in the present study are able to suppress the algal pathogens Algicola bacterio lytica and Pseudoalteromonas elyakovii.…”

Section: Bioactivity Of Metabolites Produced Bymentioning

confidence: 64%

Beneficial effects of 2,4-diacetylphloroglucinol- producing pseudomonads on the marine alga Saccharina latissima

Nagel¹,

Schneemann²,

Kajahn³

et al. 2012

Aquat. Microb. Ecol.

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Pseudomonas strains were shown to be regularly associated with the brown macroalga Saccharina latissima from the Baltic Sea, studied over several years, and were identified as producers of the antimicrobially active compound 2, 4-diacetylphloroglucinol. These findings support the assumption of a stable association between the Pseudomonas spp. strains and S. latissima in the Baltic Sea. The metabolite profile of the Pseudomonas spp. comprised mono acetylphloroglucinol, 2, 4-diacetylphloroglucinol, pyoluteorin and several rhizoxins, which exhibited broad-spectrum antibiotic activities against Gram-positive and Gram-negative bacteria as well as against fungi. Because the antibiotic activities included the inhibition of the 2 algal pathogens Pseudoalteromonas elyakovii and Algicola bacteriolytica, we propose a beneficial effect of these marine pseudomonads on their host S. latissima. KEY WORDS:Pseudomonas protegens · Alga-bacteria association · 2, 4-diacetylphloroglucinol · Pyoluteorin · Rhizoxin · Brown macroalgae Resale or republication not permitted without written consent of the publisher

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“…Compound 1 is identical to WF-1360C (20,21), a previously reported analog of the antimitotic agent rhizoxin (Fig. 3).…”

Section: Identification Of New Rhizoxin Analogs Marine Bacterial Isomentioning

confidence: 99%

Identification and Characterization of Novel Antimitotic Compounds for the Treatment of Breast Cancer

Roberge¹

2002

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A new antitumor complex, WF-1360, WF-1360A, B, C, D, E and F.

Cited by 56 publications

References 1 publication

Isolation and Identification of Rhizoxin Analogs from Pseudomonas fluorescens Pf-5 by Using a Genomic Mining Strategy

Isolation and Identification of Rhizoxin Analogs from Pseudomonas fluorescens Pf-5 by Using a Genomic Mining Strategy

Beneficial effects of 2,4-diacetylphloroglucinol- producing pseudomonads on the marine alga Saccharina latissima

Identification and Characterization of Novel Antimitotic Compounds for the Treatment of Breast Cancer

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