THE HALIDE METABOLISM OF STREPTOMYCES AUREOFACIENS MUTANTS. THE BIOSYNTHESIS OF 7-CHLORO-, 7-CHLORO³⁶- AND 7-BROMOTETRACYCLINE AND TETRACYCLINE

Abstract

Our intermediate values check closely with some l-halo-2-indanones8 which should have the same halo-carbonyl geometry (III) since the five membered ring has four carbon atoms which must be in one plane and a fifth, the carbonyl group, which can maintain favorable bisections with the «-substituents by remaining in the plane. Ill IV I I state, since the repulsive forces in Cl-C-C-C©II with a full negative charge on oxygen must be considerable even though the geometry is not quite the same as in a-chlorocyclopentanone.The framework outlined previously2 and herein will accommodate recent comments on the puckered cyclopentane ring,9•10 while LeFevre's recent polarizability data11 are also in general argeement.

Bromomonamycins, Unnatural Analogues of the Monamycin Cyclodepsipeptide Antibiotics: Production, Isolation, and Biological Activity

“…In the tetracycline and griseofulvin fermentations (3,6), chloride was preferentially incorporated when both chloride and bromide were present in the growth medium. With chloramphenicol, the situation differed, and the bromide competed with the chloride to an extent which depended on the ratio of the two ions in solution (8).…”

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“…The biosynthetic substitution of bromine for chlorine has been achieved in a number of antibiotic substances (3,6,8). After the addition of inorganic bromide to a dechlorinated medium, Streptomyces aureofaciens produced bromotetracycline (3), and Penicillium griseofulvum and P. nigricans produced bromogriseofulvin (6).…”

Bromobalhimycin and Chlorobromobalhimycins—Illuminating the Potential of Halogenases in Glycopeptide Antibiotic Biosyntheses

“…Our experiments are based on the total substitution of chloride by the other halogenide salts fluoride, bromide,8 and iodide in the culture media of Amycolatopsis balhimycina 9 (formerly assigned as Amycolatopsis mediterranei 10), the strain producing vancomycin‐type balhimycin ( 1 ; Scheme ). Bromide supplementation was originally described for griseofulvin,11 tetracyclin,12 and bromothricin 13. While fluoride and iodide supplementation proved toxic to A. balhimycina cultures, fermentation with bromide salts yielded an antibiotically active compound.…”

Biosynthesis of the Tetracycline Antibiotics

“…When care is taken to exclude chloride ion from the medium, normally halogenating strains produce unhalogenated tetracyclines in undiminished quantity. Some strains will accept bromide ion as a substitute and thus produce bromotetracycline (I,RI = Br) (26)(27)(28)(29). This substance is quite active biologically though it has not found clinical application.…”