Microbial transformation of aklanonic acid, a potential early intermediate in the biosynthesis of anthracyclines.

Wagner, Christina; Eckardt, K.; Schumann, G.; Ihn, W.; Tresselt, D.

doi:10.7164/antibiotics.37.691

Cited by 43 publications

(18 citation statements)

References 7 publications

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“…An inability of 2-OH-aklanonic acid to enter the cells is unlikely, because Eckardt e t al. (1985b) and Wagner et al (1984) succeeded in converting aklanonic acid to aglycones by biotransformation.…”

Section: Discussionmentioning

confidence: 99%

Isolation and characterization of aclacinomycin A-non-producing Streptomyces galilaeus (ATCC 31615) mutants

et al. 1994

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Twelve mutants of Streptomyces galilaeus (ATCC 31615) blocked in the production of aclacinomycin A, an anthracycline antibiotic with significant antitumour activity, accumulated intermediates of the biosynthesis of aclacinomycins and several anthracyclines with variant sugar moieties. Three of these aklavinone glycosides have not been described before. Mutant strains H028, H061 and H036 were blocked before the formation of aklavinone, a common intermediate for most anthracyclines. Strain H039 accumulated aklavinone and H026, H035, H038 and H054 had mutations that changed glycosylation of aklavinone. Characterization of the mutants and their products is described.

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Section: Discussionmentioning

confidence: 99%

Isolation and characterization of aclacinomycin A-non-producing Streptomyces galilaeus (ATCC 31615) mutants

et al. 1994

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“…caesius 2118 were found to produce anthracyclines and anthracyclinones when aklanonic acid was added t o the cultures under the conditions found t o be optimal in previous experiments with mutants of Str. griseus (WAGNER et al 1984).…”

Section: Resultsmentioning

confidence: 99%

“…Our previous experiments with blocked mutants of Streptomyces griseus showed that the anthracyclinone-related metabolite aklanonic acid with its incomplete carbon skeleton can serve as a precursor in the biosynthesis of structurally different types of anthracyclinones (WAGNER et al 1984, ECKARDT et al 1985. We, therefore, were interested t o find out whether aklanonic acid is also transformed by other species of Streptomyces known as producers of anthracyclines.…”

Section: Discussionmentioning

confidence: 99%

“…According to results obtained with the radioactively labelled precursor aklanonic acid was completely incorporated into the molecules of the conversion products. (WAGNER et al 1984, ECKARDT et al 1985. On the basis of these results we suggested that aklanonic acid might be en early key intermediate in the biosynthesis of all anthracyclines independent of the producing organism.…”

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confidence: 88%

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Biotransformation of aklanonic acid by blocked mutants of anthracycline‐producing strains of Streptomyces galilaeus and Streptomyces peucetius

Schumann¹,

Stengel²,

Eckardt³

et al. 1986

J. Basic Microbiol.

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Aklanonic acid is an anthracyclinone-related pigment that was found to be an intermediate at an early stage of the biosynthesis of daunomycinone glycosides by Streptomyces griseus. We now isolated anthracycline-negative mutants of other Streptomyces species and used them in feeding experiments with both natural and radioactive aklanonic acid. In cultures of the mutant Streptomyces galilaeus S 727 exogenous aklanonic acid was biotransformed to cinerubin A as the major product. The spectrum of the conversion products was qualitatively comparable to that of the parent strain. In cultures of mutant 21/8 derived from Streptomyces peucetius var. caesius the predominant conversion product was epsilon-rhodomycinone. Daunomycinone glycosides were isolated in small amounts. According to results obtained with the radioactively labelled precursor aklanonic acid was completely incorporated into the molecules of the conversion products. Our findings suggest that aklanonic acid is also a natural intermediate in the biosynthesis of anthracyclines by Streptomyces galilaeus and Streptomyces peucetius. Proposed biosynthetic pathways have been constructed.

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“…From biosynthetic studies, many intermediates have been isolated and their roles in the biosynthesis of anthracyclines have been clarified (16,31,35). There is also some understanding of the enzymatic steps in the biosynthetic pathway (11).…”

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confidence: 99%

Molecular cloning and characterization of the aklavinone 11-hydroxylase gene of Streptomyces peucetius subsp. caesius ATCC 27952

et al. 1994

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The gene encoding aklavinone 11-hydroxylase of Streptomyces peucetius subsp. caesius ATCC 27952 was cloned and sequenced. The deduced amino acid sequence of the gene contains at least two common motifs of well-conserved amino acid sequences of several flavin-type bacterial hydroxylases. The hydroxylase gene is apparently transcribed from a single transcriptional start point. The phenotype of a dnrF mutant generated by gene disruption supports the idea that the dnrF gene encodes aklavinone 11-hydroxylase.

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Microbial transformation of aklanonic acid, a potential early intermediate in the biosynthesis of anthracyclines.

Cited by 43 publications

References 7 publications

Isolation and characterization of aclacinomycin A-non-producing Streptomyces galilaeus (ATCC 31615) mutants

Isolation and characterization of aclacinomycin A-non-producing Streptomyces galilaeus (ATCC 31615) mutants

Biotransformation of aklanonic acid by blocked mutants of anthracycline‐producing strains of Streptomyces galilaeus and Streptomyces peucetius

Molecular cloning and characterization of the aklavinone 11-hydroxylase gene of Streptomyces peucetius subsp. caesius ATCC 27952

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