An Enzyme Inhibitor, Panosialin, Produced by Streptomyces. Ii

Kumagai, M.; Suhara, Yasuji; Aoyagi, Takaaki; Umezawa, Hamao

doi:10.7164/antibiotics.24.870

Cited by 23 publications

(7 citation statements)

References 29 publications

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“…However, there are only a few reports of phenolic lipids isolated from actinomycetes, a Streptomyces sp. (25) and Mycobacterium leprae (26). Panosilains (25), such as 5-(13-methyltetradecyl)benzene-1,3-diol, were isolated as inhibitors of a viral sialidase.…”

Section: Discussionmentioning

confidence: 99%

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Phenolic Lipids Synthesized by Type III Polyketide Synthase Confer Penicillin Resistance on Streptomyces griseus

Funabashi

Funa

Horinouchi

2008

Journal of Biological Chemistry

110

114

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Type III polyketide synthases (PKSs) found in plants, fungi, and bacteria synthesize a variety of aromatic polyketides. A Gram-positive, filamentous bacterium Streptomyces griseus contained an srs operon, in which srsA encoded a type III PKS, srsB encoded a methyltransferase, and srsC encoded a flavoprotein hydroxylase. Consistent with this annotation, overexpression of the srs genes in a heterologous host, Streptomyces lividans, showed that SrsA was a type III PKS responsible for synthesis of phenolic lipids, alkylresorcinols, and alkylpyrones, SrsB was a methyltransferase acting on the phenolic lipids to yield alkylresorcinol methyl ethers, and SrsC was a hydroxylase acting on the alkylresorcinol methyl ethers. In vitro SrsA reaction showed that SrsA synthesized alkylresorcinols from acyl-CoAs of various chain lengths as a starter substrate, one molecule of methylmalonyl-CoA, and two molecules of malonyl-CoA. SrsA was thus unique in that it incorporated the extender substrates in a strictly controlled order of malonylCoA, malonyl-CoA, and methylmalonyl-CoA to produce alkylresorcinols. An srsA mutant, which produced no phenolic lipids, was highly sensitive to ␤-lactam antibiotics, such as penicillin G and cephalexin. Together with the fact that the alkylresorcinols were fractionated mainly in the cell wall fraction, this observation suggests that the phenolic lipids, perhaps associated with the cytoplasmic membrane because of their amphiphilic property, affect the characteristic and rigidity of the cytoplasmic membrane/peptidoglycan of a variety of bacteria. An srs-like operon is found widely among Gram-positive and -negative bacteria, indicating wide distribution of the phenolic lipids.Type III PKSs 2 are structurally and functionally simple PKSs that catalyze the synthesis of aromatic polyketides in both plants and microorganisms (1). We previously found that a type III PKS, RppA, in the Gram-positive, filamentous bacterium Streptomyces griseus catalyzes the synthesis of 1,3,6,8-tetrahydroxynaphthalene by using malonyl-CoA as a starter, carrying out four successive extensions with malonyl-CoA and cyclizing the resulting pentaketide to the naphthalene scaffold (2). This was the first report of a functional type III PKS from bacteria. Since then, genome projects of bacteria have predicted that type III PKSs are distributed widely not only in Streptomyces but also other various bacteria. For example, ArsB and ArsC, both of which are type III PKSs in Azotobacter vinelandii, catalyze the synthesis of alkylresorcinols and alkylpyrones, respectively, which are essential for encystment as the major lipids in the cyst membrane (3).We have recently completed the genome project for S. griseus 3 and found another gene encoding a type III PKS, in addition to RppA. This type III PKS was named SrsA (Streptomyces resorcinol synthesis) because of its ability to synthesize alkylresorcinols in a unique manner (see below). SrsA, showing 31% amino acid sequence identity to RppA, appeared to be a member of the proteins whose synth...

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Section: Discussionmentioning

confidence: 99%

“…(25) and Mycobacterium leprae (26). Panosilains (25), such as 5-(13-methyltetradecyl)benzene-1,3-diol, were isolated as inhibitors of a viral sialidase. We speculate that panosilains are synthesized by an SrsA-like enzyme, because they are similar in chemical structure to compounds 9-11.…”

Section: Discussionmentioning

confidence: 99%

Phenolic Lipids Synthesized by Type III Polyketide Synthase Confer Penicillin Resistance on Streptomyces griseus

Funabashi

Funa

Horinouchi

2008

Journal of Biological Chemistry

110

114

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“…The phenols are 5-n-alkylresorcinols and their galactoside derivatives, 6-n-alkylresorcylic acids and 5-(2-hydroxy-alkyl)resorcinols. Long-chain alkylresorcinols have been detected in many species of plants (12,13,33,34), and similar compounds also have been detected in Mycobacterium leprae (8,10) and Streptomyces species (19). 5-nheneicosylresorcinol and 5-n-nonadecylresorcinol also have been identified in A. chrococcum (2).…”

Section: -Ar4mentioning

confidence: 99%

Isolation and characterization of several unique lipids from Azotobacter vinelandii cysts

Su¹,

Reusch²,

Sadoff³

1981

J Bacteriol

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Unique cyclic compounds were found in the lipid fraction of Azotobacter vinelandii cysts. In addition to two major molecular species which had already been identified, 5-n-alkylresorcinol and its galactoside derivative, five other molecular species (two alkyl side chain homologs of each) were isolated, and their structures were established by infrared, ultraviolet, nuclear magnetic resonance, and mass spectroscopy. These 10 compounds were 6-n-heneicosylresorcylic acid methyl ester and 6-n-tricosylresorcylic acid methyl ester, 5-n-(2-hydroxy)heneicosylresorcinol and 5-n-(2-hydroxy)tricosylresorcinol, 5-n-heneicosyl-4-acetylresorcinol and 5-n-tricosyl-4-acetylresorcinol, 6-n-heneicosyl-4-hydroxypyran-2-one and 6-n-tricosyl-4-hydroxypyran-2-one, and 6-(2-oxotricosyl)-4-hydroxy-pyran-2one and 6-(2-oxopentacosyl)-4-hydroxypyran-2-one. Azotobacter vinelandii is a gram-negative, free-living, nitrogen-fixing bacterium that inhabits the soil. Exponentially growing cells appear as large ovoid rods under a microscope. At the end of exponential growth, a small percentage of cells undergo differentiation, resulting in the formation of cysts, which are metabolically dormant cells. They are more resistant to deleterious physical conditions than are vegetative cells (31). Microscopically, mature cysts appear as round, refractile, nonmotile cells made up of three major components, the exine, intine, and central body (15, 22). Encystment of A. vinelandii can be induced by transferring exponentially growing vegetative cells from glucose to 0.2% fB-hydroxybutyrate. The entire encystment process is completed within 4 to 6 days and results in the conversion of more than 90% of the vegetative cells into cysts (21). ,8-Hydroxybutyrate serves as both a carbon source and an energy source during the encystment. Encystment requires that cells change from carbohydrate to lipid metabolism, and thus it seemed reasonable to study the lipid composition of cysts. Lin and Sadoff (23) found that cysts contain twice as much lipid as do vegetative cells on a dry weight basis. A wide variety of fatty acids are found in cysts (23), whereas only four major fatty acids are present in vegetative cells (16). In an investigation of cyst lipids, Reusch and Sadoff (29) fractionated them into neutral lipids, "glycolipids," and phospholipids on a silicic acid MATERIALS AND METHODS Growth of bacteria. A. vinelandii ATCC 12837 was used throughout this study. Cells were cultivated in Burk nitrogen-free medium (36) with either 1% glucose or 1% sodium acetate as the carbon source. The culture was incubated at 30°C with shaking. Growth was monitored by measuring the optical density at 620 nm with a spectrophotometer. Induction of encystment. Encystment was induced by the method of Lin and Sadoff (21). Exponentially growing cells (optical density, 0.7) were harvested by centrifugation, washed once with Burk buffer (medium without a carbon source), and suspended in the same volume of Burk buffer. fi-Hydroxybutyrate was added to a final concentration of 0.2%, and the cu...

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“…Only panosialin as a phenolic sulfate derivative was isolated from Streptomyces. 7,8 Herein we report the isolation, structure elucidation and biological activities of these compounds (1-3). 3).…”

Section: Introductionmentioning

confidence: 99%

Two new stemphol sulfates from the mangrove endophytic fungus Stemphylium sp. 33231

et al. 2015

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Two new stemphol sulfates, stemphol A (1) and stemphol B (2), along with known compound stemphol (3) were isolated from the EtOAc extract of the fermentation of an endophytic Stemphylium sp. 33231. The structures of these compounds were elucidated on the basis of spectroscopic analysis. The isolated compounds exhibited potent antibacterial activities against six terrestrial pathogenic bacteria with MIC values of 0.6-10 μg ml(-1). The inhibitory activities of all compounds against five cancer cell lines were evaluated.

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An Enzyme Inhibitor, Panosialin, Produced by Streptomyces. Ii

Cited by 23 publications

References 29 publications

Phenolic Lipids Synthesized by Type III Polyketide Synthase Confer Penicillin Resistance on Streptomyces griseus

Phenolic Lipids Synthesized by Type III Polyketide Synthase Confer Penicillin Resistance on Streptomyces griseus

Isolation and characterization of several unique lipids from Azotobacter vinelandii cysts

Two new stemphol sulfates from the mangrove endophytic fungus Stemphylium sp. 33231

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