Effect of Exogenous Penicillin on Penicillin Biosynthesis

Gordee, E. Z.; Day, L. E.

doi:10.1128/aac.1.4.315

Cited by 32 publications

(11 citation statements)

References 20 publications

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“…The results suggested that the antibiotic was regulating its own synthesis but by an unkilown mechanism. A similar phenomenon was observed in the biosynthesis of penicillin by Penicilliut71 clzrysogenwn (7). Therefore, the effect of chloramphenicol on the synthesis of arylamine synthetase in Streptomyces sp.…”

Section: Repression Of Drylamine Synthetasesupporting

confidence: 72%

Regulation of chloramphenicol synthesis in Streptomyces sp. 3022a. Properties of arylamine synthetase, an enzyme involved in antibiotic biosynthesis

Jones¹,

Westlake²

1974

Can. J. Microbiol.

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A new arylamine synthetase activity has been demonstrated in Streptomyces sp. 3022a when grown under chloramphenicol-producing conditions. The enzyme has several characteristics which distinguish it from anthranilate synthetase. It converts chorismic acid to an, as yet, unidentified aromatic amine easily separable from anthranilic and p-aminobenzoic acids. This arylamine synthetase was absent from strains of Streptomyces sp. 3022a, which were incapable of chloramphenicol production. The addition of chloramphenicol to growing cultures repressed arylamine synthetase but not anthranilate synthetase activity. The role of arylamine synthetase in the control and regulation of chloramphenicol biosynthesis is discussed.

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Section: Repression Of Drylamine Synthetasesupporting

confidence: 72%

Regulation of chloramphenicol synthesis in Streptomyces sp. 3022a. Properties of arylamine synthetase, an enzyme involved in antibiotic biosynthesis

Jones¹,

Westlake²

1974

Can. J. Microbiol.

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“…However, if compartmentation exists in P. chrysogenum, it is possible that high penicillin concentrations exist in such a compartment. High levels of penicillin are also required to inhibit net penicillin synthesis in intact mycelia of P. chrysogenum (7), but this could be due to a permeation problem.…”

Section: Discussionmentioning

confidence: 99%

Insensitivity of Homocitrate Synthase in Extracts of Penicillium chyrosogenum to Feedback Inhibition by Lysine1

Masurekar¹,

Demain²

1974

Applied Microbiology

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We previously reported that lysine inhibits in vivo homocitrate synthesis in the lysine bradytroph, Penicillium chrysogenum L1, and that such feedback inhibition could explain the known lysine inhibition of penicillin formation. In the present study, it was found that dialyzed cell-free extracts of mutant L1 converted [1-"4C ]acetate to homocitrate. This homocitrate synthase activity was extremely labile but could be stabilized by high salt concentrations. The pH optimum of the reaction was 6.9, and the Km was 5.5 mM with respect to a-ketoglutarate. The reaction was also dependent upon the presence of Mg2+, adenosine 5'-triphosphate, and coenzyme A. Surprisingly, the activity in these crude extracts was not inhibited by lysine. Benzylpenicillin at a high concentration (20 mM) partially inhibited the enzyme, an effect that was enhanced by lysine. Casein hydrolysate also partially inhibited the enzyme. Penicillin and L-lysine appear to share a branched biosynthetic pathway in Penicillium chrysogenum (4a). The inhibition of penicillin production by lysine (3) might thus be explained by feedback inhibition of the first enzyme of the common path, homocitrate synthase, by lysine. In support of this hypothesis, we reported that addition of lysine to washed suspensions of P. chrysogenum inhibited incorporation of labeled valine into the antibiotic (16). To elucidate the site of lysine action, we isolated a lysine bradytrophic mutant of the penicillin-producing strain Wis. 54-1255. We have found that in vivo homocitrate accumulation in this early-blocked mutant is inhibited by lysine (4b). In the present communication, we report studies on homocitrate synthase activity in crude extracts of this mutant. Surprisingly, such activity is insensitive to lysine inhibition. MATERIALS AND METHODS Culture. The lysine bradytroph, P. chrysogenum L,, was obtained by mutagenesis of P. chrysogenum Wis. 54-1255 (4b). It was maintained on slants of Sabouraud dextrose agar (Difco Laboratories, Inc., Detroit, Mich.) with 0.1% yeast extract. Preparation of mycelia. Conidia of mutant L, from a slant were inoculated into 50 ml of Sabouraud ' Contribution no.

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“…5-Chloro-l-(2,3,5-tri-0-acetyl-/9-D-ribofuranosyl)imidazole-4-carboxamidoxime (22). A mixture of 10 (5.07 g, 13.14 mmol), absolute ethanol (25 ml), and hydroxylamine (0.48 g) was refluxed over a steam bath for 1 h. More hydroxylamine (0.48 g) was added and the clear reaction solution was refluxed for a further 2 h. It was left at room temperature overnight.…”

Section: Methodsmentioning

confidence: 99%

“…To evaluate the in vivo therapeutic effect of 16, a guinea pig skin infection model was used. 22 This nucleoside was formulated in either polyethylene glycol "300" or in propylene glycol (20%), 70% sorbitol (3%), and ethyl alcohol to 100 ml at a 5% (w/v) concentration.…”

mentioning

confidence: 99%

Synthesis and antiviral and antimicrobial activity of certain 1-.beta.-D-ribofuranosyl-4,5-disubstituted imidazoles

Srivastava¹,

Streeter²,

Matthews³

et al. 1976

J. Med. Chem.

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Starting with AICA ribonucleoside the following nucleosides were prepared. Methyl 5-amino-1-(2,3,5-tri-O-acetyl-beta-D-ribofuranosyl)imidazole-4-carboxylate (5) was converted into methyl 5-chloro-1-(2,3,5-tri-O-acetyl-beta-D-ribofuranosyl)imidazole-4-carboxylate (6) via diazotization in the presence of cuprous chloride. Similarly, 5-amino-1-(2,3,5-tri-O-acetyl-beta-D-ribofuanosyl)imidazole-4-carbonitrile (9) was converted into 5-chloro-, 5-bromo-, and 5-iodo-1-(2,3,5-tri-O-acetyl-beta-D-ribofuranosyl)imidazole-4-carbonitrile derivatives. These 5-halogenated imidazole nucleosides were treated with several nucleophiles such as ammonia, hydroxylamine, and hydrogen sulfide to provide, respectively, 5-haloimidazole-4-carboxamide, 5-haloimidazole-4-carboxamidoxime, and 5-haloimidazole-4-thiocarboxamide ribonucleosides. 5-Chloro- or 5-bromo-1-(2,3,5-tri-O-acetyl-beta-D-ribofuranosyl)imidazole-4-carbonitrile was treated with potassium hydrosulfide to yield 5-mercapto-1-beta-D-ribofuranosylimidazole-4-thiocarboxamide (16). The catalytic reduction of 5-chloro- or 5-bromo-1-beta-D-ribofuranosylimidazole-4-carboxamidoxime provided 1-beta-D-ribofuranosylimidazole-4-carboxamidines as their hydrochloride and hydrobromide salts, respectively. These nucleosides were tested for in vitro antiviral, antifungal, and antibacterial activity. The 5-halo analogues of 1-beta-D-ribofuranosylimidazole-4-carboxamide showed significant antiviral activity whereas compound 16 was found inhibitory to fungi.

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Effect of Exogenous Penicillin on Penicillin Biosynthesis

Cited by 32 publications

References 20 publications

Regulation of chloramphenicol synthesis in Streptomyces sp. 3022a. Properties of arylamine synthetase, an enzyme involved in antibiotic biosynthesis

Regulation of chloramphenicol synthesis in Streptomyces sp. 3022a. Properties of arylamine synthetase, an enzyme involved in antibiotic biosynthesis

Insensitivity of Homocitrate Synthase in Extracts of Penicillium chyrosogenum to Feedback Inhibition by Lysine1

Synthesis and antiviral and antimicrobial activity of certain 1-.beta.-D-ribofuranosyl-4,5-disubstituted imidazoles

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