Verticilactam, a New Macrolactam Isolated from a Microbial Metabolite Fraction Library

Nogawa, Toshihiko; Okano, Akiko; Takahashi, Shunji; Uramoto, Masakazu; Konno, Hiroyuki; Saito, Tamio; Osada, Hiroyuki

doi:10.1021/ol1018618

Cited by 40 publications

(22 citation statements)

References 11 publications

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“…The core structure of the macrotermycins ( 5 ) belongs to a family of macrolactam polyketides that include incednine, 10 vicenistatin, 11 silvalactam, 12 heronamides, 13 verticilactam, 14 ciromicins, 15 mirilactams and lobosamides. 16 Both 1 and 3 can be viewed as polyene precursors for intramolecular cycloadditions leading to 2 and 4 , respectively, and the relevant reaction pathways, whether enzymatically catalyzed or occurring spontaneously either in situ or during purification, are being investigated.…”

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Macrotermycins A–D, Glycosylated Macrolactams from a Termite-Associated Amycolatopsis sp. M39

et al. 2017

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Bioassay-guided metabolomic analyses led to the characterization of four new 20-membered glycosylated polyketide macrolactams – macrotermycins A-D – from a termite-associated actinomycete, Amycolatopsis sp. M39. M39’s sequenced genome revealed the macrotermycin’s putative biosynthetic gene cluster. Macrotermycins A and C had antibacterial activity against human-pathogenic S. aureus and of greater ecological relevance, they also had selective antifungal activity against a fungal parasite of the termite fungal garden.

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Macrotermycins A–D, Glycosylated Macrolactams from a Termite-Associated Amycolatopsis sp. M39

et al. 2017

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“…To discover novel natural products that are normally expressed at a very low level, we have been performing a systematic isolation of secondary metabolites. As a result, we isolated verticilactam 4 from Streptomyces spiroverticillatus JC-8444, a tautomycin producer, 5 and 6-dimethylallylindole-3-carbaldehyde 6 from S. reveromyceticus SN-593, a reveromycin producer. 7 In addition, from S. reveromyceticus SN-593, we detected metabolites showing UV spectra similar to furaquinocin (FQ), but different mass from the reported FQs.…”

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confidence: 99%

Furaquinocins I and J: novel polyketide isoprenoid hybrid compounds from Streptomyces reveromyceticus SN-593

et al. 2011

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Two novel furaquinocin (FQ) analogues, I (1) and J (2), were isolated from Streptomyces reveromyceticus SN-593 strain NRM2. Their structures were elucidated by MS and NMR analyses. Similar to the previously described FQ D (3), both 1 and 2 possessed a dihydrofuran ring fused to a polyketide naphthoquinone skeleton. The main difference between 1, 2 and 3 was the type of residue attached to C-13; these were a carboxyl, a carboxamide and a methyl residue, respectively. INTRODUCTIONThe majority of bioactive compounds used as drugs and bioprobes originally derive from the secondary metabolites of microorganisms. Genome sequence analyses have shown that the number of bioactive compounds isolated from Streptomyces spp. is much lower than the number of gene clusters harbored by each species. [1][2][3] This indicates that the majority of gene clusters are either not expressed, or are only minimally expressed, under standard laboratory conditions. To discover novel natural products that are normally expressed at a very low level, we have been performing a systematic isolation of secondary metabolites. As a result, we isolated verticilactam 4 from Streptomyces spiroverticillatus JC-8444, a tautomycin producer, 5 and 6-dimethylallylindole-3-carbaldehyde 6 from S. reveromyceticus SN-593, a reveromycin producer. 7 In addition, from S. reveromyceticus SN-593, we detected metabolites showing UV spectra similar to furaquinocin (FQ), but different mass from the reported FQs. Consistent with the finding, we could annotate an FQ biosynthetic gene cluster from the genome draft sequence. However, with the quantity produced by wild type strain, it was not possible to isolate and determine the structure. So, in order to improve the production of novel FQ derivatives, we performed the expression of pathway-specific regulatory genes associated with the FQ biosynthetic gene cluster. Activation of pathwayspecific positive regulatory gene is commonly used for augmentation of secondary metabolites in Streptomyces. [8][9][10] FQs, originally isolated from the culture broth of Streptomyces sp. 11 have cytocidal activities without antibacterial activity. So far, eight analogues of these polyketide isoprenoid hybrid compounds (Figure 1) [11][12][13] and their gene cluster 14 have been identified.

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“…Thus, we constructed a microbial metabolite fraction library by systematic separation with a spectral database, based on photodiode-array detector attached LC/MS analysis to discover structurally unique metabolites efficiently and rapidly. We discovered and isolated verticilactam 6 from S. spiroveticillatus JC-8444, a tautomycin producer, [7][8][9] and the new fraquinocins I and J 10 and 6-dimethylalylindole-3-carbaldehyde 11 from S. reveromyceticus SN-593, a reveromycin producer 12 by our methodology constructing the fraction library. Also, Bugni et al 13 reported a marine natural products library by HPLC-MS fractionation for rapid drug discovery.…”

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confidence: 99%

Spirotoamides A and B, novel 6,6-spiroacetal polyketides isolated from a microbial metabolite fraction library

et al. 2011

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Two new 6,6-spiroacetal polyketides, spirotoamides A (1) and B (2), were isolated from a microbial metabolite fraction library of Streptomyces griseochromogenes JC82-1223 by screening of structurally unique compounds based on a search of spectral database. The fraction library was constructed using a systematic separation method to efficiently discover new metabolites from microbial sources such as actinomycetes and fungi. The structures of 1 and 2 were elucidated by 2D-NMR and mass spectrometric measurements. They belong to a class of polyketides, and contain a 6,6-spiroacetal core structure and a carboxamide group. The biosynthetic pathway of 1 and 2 is discussed in the text. Keywords: fraction library; microbial metabolite; spiroacetal polyketide; Streptomyces griseochromogenes; structure elucidation INTRODUCTION Microorganisms, such as actinomycetes and fungi, have a tremendous capacity to produce structurally diverse metabolites 1 with disparate activities, rendering them a significant source of pharmaceutical leads and therapeutic agents. 2,3 They are also used as potential bioprobes for chemical biology studies. 4,5 Many secondary metabolites have been reported, but not all have been isolated, nor have their wide-ranging physicochemical properties and low abundance been examined with regard to their potentially useful activities. Thus, we constructed a microbial metabolite fraction library by systematic separation with a spectral database, based on photodiode-array detector attached LC/MS analysis to discover structurally unique metabolites efficiently and rapidly. We discovered and isolated verticilactam 6 from S. spiroveticillatus JC-8444, a tautomycin producer, 7-9 and the new fraquinocins I and J 10 and 6-dimethylalylindole-3-carbaldehyde 11 from S. reveromyceticus SN-593, a reveromycin producer 12 by our methodology constructing the fraction library. Also, Bugni et al. 13 reported a marine natural products library by HPLC-MS fractionation for rapid drug discovery. These reports have demonstrated the advantage of fraction libraries in isolating and investigating the activities of natural products.Our microbial fraction library was developed on basic chromatographic techniques, comprizing two-step separation by middlepressure liquid chromatography (MPLC) and C 18 -HPLC, yielding 300-400 fractions from a single microbial strain with reproducibility. In addition to many known compounds, the fractions, which contain unidentified minor components, might contain valuable compounds

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Verticilactam, a New Macrolactam Isolated from a Microbial Metabolite Fraction Library

Cited by 40 publications

References 11 publications

Macrotermycins A–D, Glycosylated Macrolactams from a Termite-Associated Amycolatopsis sp. M39

Macrotermycins A–D, Glycosylated Macrolactams from a Termite-Associated Amycolatopsis sp. M39

Furaquinocins I and J: novel polyketide isoprenoid hybrid compounds from Streptomyces reveromyceticus SN-593

Spirotoamides A and B, novel 6,6-spiroacetal polyketides isolated from a microbial metabolite fraction library

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