Nucleoside antibiotics. Biosynthesis of the maleimide nucleoside antibiotic, showdomycin, by Streptomyces showdoensis

Elstner, Erich F.; Suhadolnik, Robert J.

doi:10.1021/bi00795a019

Cited by 25 publications

(19 citation statements)

References 22 publications

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“…In the biosynthesis of pseudouridine, the intramolecular rearrangement in tRNA of uridylate to pseudouridylate has been strongly suggested.1-6) The biosynthesis of showdomycin has been well established and confirmed to occur by the condensation of ribose and an asymmetric four-carbon dicaboxylic acid. [7][8][9][10] Recently, studies on the biosynthesis of minimycin revealed a novel mechanism whereby C-riboside linkage is formed from sedoheptulose 7-phosphate (or eight-carbon branched chain sugar phosphate).11)…”

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confidence: 99%

Biosynthesis of formycin. Incorporation and distribution of labeled compounds into formycin.

et al. 1976

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1. Two carbons, carbon-2 and one of carbons-3 to -5, of lysine seemed likely to be incorporated into one of carbon of the chromophore moiety of formycin.2. From the results of radioisotopic studies with glutamate, r-amino-n-butyrate or organic acids related to tricarboxylic acid cycle, the important role of glutamate in the biosynthesis of formycin was strongly suggested.3. The incorporation of nitrogen(s) of lysine into three nitrogens, including two nitrogens of pyrazole ring, of formycin was suggested by mass spectroscopy. 4. Ribose was estimated as a direct precursor for the ribosyl moiety of formycin, whereas the biosynthesis of ribose was shown to occur via the pathway other than hexose monophosphate shunt or glucuronate pathway.5. In replacement culture, the salvage synthesis of formycin from its chromophore moiety was not observed and it was also evident that the chromophore moiety or pyrazofurin (pyrazomycin) inhibited the biosynthesis of formycin.There have been several investigations on the biosynthesis of C-riboside nucleosides, i.e., pseudouridine, showdomycin, minimycin, pyrazofurin (pyrazomycin) and the formycin family. In the biosynthesis of pseudouridine, the intramolecular rearrangement in tRNA of uridylate to pseudouridylate has been strongly suggested.1-6) The biosynthesis of showdomycin has been well established and confirmed to occur by the condensation of ribose and an asymmetric four-carbon dicaboxylic acid.7-10)Recently, studies on the biosynthesis of minimycin revealed a novel mechanism whereby C-riboside linkage is formed from sedoheptulose 7-phosphate (or eight-carbon branched chain sugar phosphate).11) C-Riboside linkage of pyrazofurin was also believed to be formed by this mechanism.11)The biosynthesis of formycin by Nocardia interforma has been proposed to occur via a pathway other than that of biosynthesis of purine nucleotide while exogeneously added ribose was estimated to be incorporated into the ribosyl moiety of formycin.12) It was also reported that formycin may be formed from formycin 5'-monophosphate then deaminated to formycin B.13) Using Streptomyces sp.MA406-A-1, a formycin-producing strain, we reported that carbon atom from lysine, glutamate and/or aspartate was incorporated into formycin with high efficiency, and that novel enzyme(s) catalyzing the amination of formycin B to formycin was present in this organism. 14,15) To elucidate the more detailed mechanism of formycin biosynthesis, we examined the incorporation and the distribution of various labeled compounds into formycin and this paper presents the results of these studies.

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Biosynthesis of formycin. Incorporation and distribution of labeled compounds into formycin.

et al. 1976

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“…These include a number of nucleotides (2,4), at least 14 nucleosides (5,6,9), and at least 6 C-substituted nucleosides (3). Biosynthetic studies of 10 nucleoside antibiotics have shown that in general either purine or pyrimidine nucleosides or nucleotides (or both), or the aglycone, serve as precursors for the nucleoside analogues elaborated by Streptomyces and fungi (7,10).…”

Section: Discussionmentioning

confidence: 99%

A9145, a New Adenine-Containing Antifungal Antibiotic: Fermentation

Boeck

Clem

Wilson

et al. 1973

Antimicrob Agents Chemother

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A9145 is a basic, water-soluble, antifungal antibiotic which is produced in a complex organic medium by Streptomyces griseolus. The metabolite has a molecular weight of 510, and contains adenine as well as sugar hydroxyl and amino groups. Although glucose, fructose, glucose polymers, and some longchain fatty acid methyl esters supported biosynthesis, oils were superior, with cottonseed oil being preferred. Several ions and salts, especially Co2+, P043-, and CaCO3, were stimulatory. Adenine, nucleosides, and some amino acids increased the accumulation of A9145 in shaken-flask fermentors. Enrichment of the culture medium with tyrosine afforded maximal enhancement of antibiotic production in both flask and tank fermentors. Control of the dissolved 02 level was also critical, the optimal concentration being 3 x 10-2 to 4.5 x 10-2 ,mole of 02/ml. Optimization of various fermentation parameters increased antibiotic titers approximately 135-fold in shaken flask fermentors and 225-fold in stirred vessels.A new antifungal antibiotic, A9145, is produced by a strain of Streptomyces griseolus, NRRL-3739, isolated from a soil sample. This basic, water-soluble antibiotic has a molecular weight of 510, contains sugar hydroxyl and amino groups, and yields one mole of adenine upon mild acid hydrolysis (R. L. Hamill and M. M. Hoehn, Abstr. 11th Intersci. Conf. Antimicrob. Ag. Chemother., p. 21, 1971 Staley Manufacturing Co.), 1.5% Nutrisoy flour (Archer-Daniels-Midland Co.), 0.2% Nadrisol (National Distiller's Products Co.), 0.2% blackstrap molasses, 0.1% CaCO3, and 2.5% agar in distilled water (final pH 6.5).Fermentor inoculum. S. griseolus was transferred aseptically, as a lyophilized pellet containing approximately 2 x 106 spores, to 250-ml widemouth Erlenmeyer flasks. These flasks contained 50 ml of a seed medium composed of 1% glucose, 3% Dextrin 700, 1.5% Nutrisoy grits (Archer-DanielsMidland Co.), 0.5% Amber BYF 300 (Amber Laboratories), 0.5% blackstrap molasses, and 0.2% CaCO3, which had been adjusted to pH 6.5 and brought to 1 liter with tap water. Incubation was with agitation on a rotary shaker at 250 rev/min (5-cm stroke) at 30 C. After 30 hr, a second seed stage, 100 ml of the seed medium in a 1-liter flask, was inoculated from the first. After an additional 24-hr incubation period under the same conditions of temperature and agitation, the second seed stage was used to inoculate fermentors with a volume of the mycelial suspension equal to 1% (v/v) of the fermentation medium.Fermentors. In initial investigations, widemouth 250-ml Erlenmeyer flasks containing 50 ml of medium were used, and incubation was as previously described. Larger-volume fermentations for supply of the metabolite were conducted in fully baffled, stirred vessels of conventional design with a total capacity of 40 liters and a 1:1 height-diameter ratio for the 25 liters of medium. Dissolved oxygen content of the broth was monitored by use of a modification of a galvanic membrane electrode previously described (1)

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“…Earlier studies on the biosynthesis of showdomycin showed that C2-to -5 of either glutamate or a-ketoglutarate served as the four-carbon precursor for the maleimide ring (Elstner and Suhadolnik, 1971a). It was not known if this four-carbon unit, following decarboxylation of a-ketoglutarate, exists as a symmetrical or asymmetrical unit when it condenses with Dribose to form showdomycin.…”

Section: Discussionmentioning

confidence: 99%

“…Maintenance of S . showdoensis cultures and isolation of showdomycin were as described (Elstner and Suhadolnik, 1971a). DE52 (exchange capacity 1 .O mequiv/g) was obtained from Reeves-Angel.…”

Section: Methodsmentioning

confidence: 99%

Nucleoside antibiotics. Asymmetric incorporation of glutamic acid and acetate into the maleimide ring of showdomycin by Streptomyces showdoensis

Elstner¹,

Suhadolnik²

1972

Biochemistry

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Nucleoside antibiotics. Biosynthesis of the maleimide nucleoside antibiotic, showdomycin, by Streptomyces showdoensis

Cited by 25 publications

References 22 publications

Biosynthesis of formycin. Incorporation and distribution of labeled compounds into formycin.

Biosynthesis of formycin. Incorporation and distribution of labeled compounds into formycin.

A9145, a New Adenine-Containing Antifungal Antibiotic: Fermentation

Nucleoside antibiotics. Asymmetric incorporation of glutamic acid and acetate into the maleimide ring of showdomycin by Streptomyces showdoensis

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