Glycocinnamoylspermidines, a new class of antibiotics. II. Isolation, physicochemical and biological properties of LL-BM123.BETA.,.GAMMA.1 and .GAMMA.2.

Martin, Jennifer H.; Kunstmann, M. P.; Barbatschi, F.; Hertz, Martin R.; Ellestad, George A.; Dann, Margaret; Redin, G. S.; Dornbush, A. C.; Kuck, N. A.

doi:10.7164/antibiotics.31.398

Cited by 26 publications

(7 citation statements)

References 5 publications

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“…(Preliminary studies indicate that the /3 form does bind to DNA.) However, the antimicrobial activity of cinodine ,B is significantly less than that of y (10), suggesting that properties of the molecule other than electrostatic charge are also related to its reactivity with DNA. Another major distinction between cinodine ,B and y is the presence in the y molecules of an additional carbonyl group in a strained heterocyclic ring associated with the terminal pentose (3).…”

Section: (2)mentioning

confidence: 84%

“…Culture turbidity continued to increase for a short period before plateauing. Microscopic Cinodine is a broad-spectrum antibiotic isolated from the fermentation broth of a Nocardia species (3,10). This antibiotic, which represents a new structural class referred to as the glycocinnamoylspermidines, consists of a trisaccharide coupled to a p-hydroxycinnamoylspermidine moiety (Fig.…”

mentioning

confidence: 99%

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Mechanism of action of cinodine, a glycocinnamoylspermidine antibiotic

Greenstein¹,

Speth²,

Maiese³

1981

Antimicrob Agents Chemother

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The mechanism of action of cinodine, a glycocinnamoylspermidine antibiotic, was investigated. Upon addition of cinodine to growing cultures of Escherichia coli, a rapid decline in viable cell numbers was observed. Culture turbidity continued to increase for a short period before plateauing. Microscopic Cinodine is a broad-spectrum antibiotic isolated from the fermentation broth of a Nocardia species (3,10). This antibiotic, which represents a new structural class referred to as the glycocinnamoylspermidines, consists of a trisaccharide coupled to a p-hydroxycinnamoylspermidine moiety (Fig. 1). As a polyamine-containing antibiotic, it is related to bleomycin (20), tallysomycin (7), and edeine (6). Three different cinodine components, /3, 7y, and y2, can be distinguished by the structure of the terminal pentose of the trisaccharide. The y2 component has an oxazolidone ring associated with the terminal sugar, whereas -y has an imidazolidone ring. The /3 form lacks the additional carbonyl group of the y components and therefore has another free amino group. The y components demonstrate an antibacterial activity that is as much as 20-fold higher than that of ,B (10; unpublished data).The unique properties of the cinodine molecules raise many interesting questions regarding structure-function relationships. This report summarizes our studies of the mechanism of antibacterial action of this antibiotic.MATERIALS AND METHODS Bacteria and bacteriophage. Escherichia coli B and AT982 dapD4 were obtained from B. Bachmann,

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Section: (2)mentioning

confidence: 84%

mentioning

confidence: 99%

Mechanism of action of cinodine, a glycocinnamoylspermidine antibiotic

Greenstein¹,

Speth²,

Maiese³

1981

Antimicrob Agents Chemother

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“…On the other hand, there are limited reports of xylosamines in glycosides. For example, some diamino xylosides have been found in certain antibiotics (36,37), one of which was isolated from members of Nocardiopsis species (36). Whether the pathogenic Bacillus species also synthesize antimicrobial xylosamine-glycosides, however, is still unclear.…”

Section: Discussionmentioning

confidence: 99%

Biosynthesis of a New UDP-sugar, UDP-2-acetamido-2-deoxyxylose, in the Human Pathogen Bacillus cereus Subspecies cytotoxis NVH 391-98

Glushka

Lee

et al. 2010

Journal of Biological Chemistry

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We have identified an operon and characterized the functions of two genes from the severe food-poisoning bacterium, Bacillus cereus subsp. cytotoxis NVH 391-98, that are involved in the synthesis of a unique UDP-sugar, UDP-2-acetamido-2-deoxyxylose (UDP-N-acetyl-xylosamine, UDP-XylNAc). UGlcNAcDH encodes a UDP-N-acetyl-glucosamine 6-dehydrogenase, converting UDP-N-acetylglucosamine (UDP-GlcNAc) to UDP-N-acetyl-glucosaminuronic acid (UDP-GlcNAcA). The second gene in the operon, UXNAcS, encodes a distinct decarboxylase not previously described in the literature, which catalyzes the formation of UDPXylNAc from UDP-GlcNAcA in the presence of exogenous NAD ؉ . UXNAcS is specific and cannot utilize UDP-glucuronic acid and UDP-galacturonic acid as substrates. UXNAcS is active as a dimer with catalytic efficiency of 7 mM ؊1 s ؊1. The activity of UXNAcS is completely abolished by NADH but unaffected by UDP-xylose. A real-time NMR-based assay showed unambiguously the dual enzymatic conversions of UDP-GlcNAc to UDP-GlcNAcA and subsequently to UDP-XylNAc. From the analyses of all publicly available sequenced genomes, it appears that UXNAcS is restricted to pathogenic Bacillus species, including Bacillus anthracis and Bacillus thuringiensis. The identification of UXNAcS provides insight into the formation of UDP-XylNAc. Understanding the metabolic pathways involved in the utilization of this amino-sugar may allow the development of drugs to combat and eradicate the disease.A food poisoning outbreak in France in 1998 led to the isolation of a new strain of Bacillus cereus subsp. cytotoxis NVH 391-98 (1). This rod-shaped Gram-positive bacterium causes a disease that initially produces emetic (nausea and vomiting)-like symptoms, and/or in more severe cases produces a diarrheal form that causes abdominal cramps and diarrhea (2). Similar to its close relatives, the notorious human pathogen Bacillus anthracis and the insecticidal Bacillus thuringiensis, the B. cereus strain can form spores. Due to its cell surface, a spore can survive harsh conditions (e.g. soil and air), and when the environment becomes appropriate, it will germinate, resulting in a vegetative cell that can produce emetic toxin and different enterotoxins (3). The cell surfaces of many pathogenic bacteria are composed of diverse and complex carbohydrate structures, some of which are known virulence factors. Indeed, different B. cereus peptidoglycans and glycoproteins were isolated, and some were reported to play a role in spore formation and infection (3-5). It is also clear, however, that among those different types of Bacillus glycans, many are not yet fully characterized. Regardless, compared with the limited knowledge of these glycan structures, the pathways leading to their biosyntheses are still elusive. To identify such metabolic pathways, we initially decided to look for putative genes encoding enzymes involved in the synthesis of glycan precursors (i.e. nucleotide-sugars).Different UDP-GlcA 2 decarboxylases with distinct functions exist in both eukaryotes...

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“…Other members of this series possess diverse structural features (456,457) such as a 4-hydroxycinnamoylspermidine moiety linked to a diaminated sugar and varied urea and guanidine substituents on the sugar residues. The structures of LL-BM123~ (273), LL-BM123Yl (274) and LL-BM123Y2 (275) were established by hydrolytic degradation and spectroscopic analyses (mainly 13C-NMR and mass spectrometry) (458) although assignment of the 13C signals of the guanidine and ureido carbonyl carbons was suggestive only.…”

Section: Other Guanidine Derivatives Originating From Microorganismsmentioning

confidence: 99%

Some Aspects of Guanidine Secondary Metabolites

Berlinck

1995

Fortschritte Der Chemie Organischer Naturstoffe / Progress in the Chemistry of Organic Natural Products

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Glycocinnamoylspermidines, a new class of antibiotics. II. Isolation, physicochemical and biological properties of LL-BM123.BETA.,.GAMMA.1 and .GAMMA.2.

Cited by 26 publications

References 5 publications

Mechanism of action of cinodine, a glycocinnamoylspermidine antibiotic

Mechanism of action of cinodine, a glycocinnamoylspermidine antibiotic

Biosynthesis of a New UDP-sugar, UDP-2-acetamido-2-deoxyxylose, in the Human Pathogen Bacillus cereus Subspecies cytotoxis NVH 391-98

Some Aspects of Guanidine Secondary Metabolites

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