Production of deoxyfrenolicin and a new antibiotic, frenolicin B by Streptomyces roseofulvus strain AM-3867.

Iwai, Yuzuru; Kora, Akiko; Takahashi, Yōko; Hayashi, Takako; Awaya, Juichi; Masuma, Rokurou; Ōiwa, Ruiko; Ōmura, Satoshi

doi:10.7164/antibiotics.31.959

Cited by 73 publications

(48 citation statements)

References 10 publications

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“…Asukamycin was also found to have anticoccidial activity. Furthermore, frenolicin B [40,41], and nanaomycins A and D [42,43], formerly isolated in our group from Streptomyces strains as antimycoplasmal and antibacterial compounds, respectively, were recently found to also show PFTase inhibitory activities [44] (for their structures see Fig. 7).…”

Section: Pftase Inhibitors Discovered By Our Screening Programmentioning

confidence: 99%

Search for Protein Farnesyltransferase Inhibitors of Microbial Origin: Our Strategy and Results as well as the Results Obtained by Other Groups

Iwasaki

Ōmura

2007

J Antibiot

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Mutant ras oncogenes are associated with various human tumors, being found in approximately 25% of all human cancers. Since its identification, the enzyme Ras protein farnesyltransferase (PFTase), which catalyzes the initial step of Ras-processing, has been viewed as a most promising target for cancer therapy. Consequently, a number of synthetic and natural small molecules have been searched and developed according to this concept during the 1990s. Among these, microbial metabolites have provided diverse structural classes of compounds which exhibit PFTase inhibitory activity. This article reviews our work on PFTase inhibitors originating from microbial metabolites, and the results of similar works carried out by several other research groups.

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Section: Pftase Inhibitors Discovered By Our Screening Programmentioning

confidence: 99%

Search for Protein Farnesyltransferase Inhibitors of Microbial Origin: Our Strategy and Results as well as the Results Obtained by Other Groups

Iwasaki

Ōmura

2007

J Antibiot

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“…A similar phenomenon has also been reported in the case of the whiE PKS (30), which produces 22-carbon and 24-carbon backbones. However, until now it has been assumed that these observations are peculiar to PKSs that exhibit relaxed chain length specificity in nature, because at least the frenolicin producer, S. roseofulvus, is known to produce both 16-and 18-carbon natural products with very similar structures (31,32). In contrast, neither the naturally occurring PKS from S. glaucescens nor any engineered PKS containing the core tcm subunits has yielded an 18-carbon product thus far.…”

Section: Discussionmentioning

confidence: 99%

Domain Analysis of the Molecular Recognition Features of Aromatic Polyketide Synthase Subunits

Zawada¹,

Khosla²

1997

Journal of Biological Chemistry

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Bacterial aromatic polyketide synthases (PKSs) are a family of homologous multienzyme assemblies that catalyze the biosynthesis of numerous polyfunctional aromatic natural products. In the absence of direct insights into their structures, the use of gene fusions can be a powerful tool for understanding the structural basis for their properties. A series of truncated and hybrid proteins were constructed and analyzed within a family of PKS subunits, designated aromatases/cyclases (ARO/ CYCs). When expressed alone, neither the N-terminal nor the C-terminal domain of the actinorhodin (act) or the griseusin (gris) ARO/CYC exhibited substantial aromatase activity. However, in the presence of each other, the half proteins were active. Furthermore, analysis of a set of hybrid proteins derived from the act and gris ARO/CYCs allowed us to localize the chain length dependence of this aromatase activity to their N-terminal domains. Unexpectedly, however, when the C-terminal domain of the gris ARO/CYC was expressed in a context where aromatase activity was absent, it could modulate the chain length specificity of the tetracenomycin (tcm) minimal PKS, leading to the formation of a novel 18-carbon product in addition to the expected 20-carbon one. It was also found that monodomain ARO/CYCs such as tcmN cannot substitute for the the N-terminal domain of didomain ARO/CYCs, even though they exhibit high sequence similarity with the N-terminal domain. Together, these results illustrate the utility of protein engineering approaches for dissecting the structure-function relationships of PKS subunits and for the generation of mutant alleles with novel biosynthetic properties.

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“…), showed anticoccidial activity against a monensin-resistant strain in vivo. Frenolicin B (12) was originally isolated as an antimycoplasmal antibiotic from Streptomyces roseofulvus by our group, 34) and later was revealed to show potent anticoccidial activity in vivo.…”

Section: )mentioning

confidence: 99%

Antiparasitic agents produced by microorganisms

Shiomi

Ōmura

2004

Proceedings of the Japan Academy. Ser. B: Physical and Biologic

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Production of deoxyfrenolicin and a new antibiotic, frenolicin B by Streptomyces roseofulvus strain AM-3867.

Cited by 73 publications

References 10 publications

Search for Protein Farnesyltransferase Inhibitors of Microbial Origin: Our Strategy and Results as well as the Results Obtained by Other Groups

Search for Protein Farnesyltransferase Inhibitors of Microbial Origin: Our Strategy and Results as well as the Results Obtained by Other Groups

Domain Analysis of the Molecular Recognition Features of Aromatic Polyketide Synthase Subunits

Antiparasitic agents produced by microorganisms

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