Stoffwechselprodukte von Actinomyceten. 9. Mitteilung. Granaticin

Corbaz, R.; Ettlinger, L.; Gäumann, E.; Kalvoda, J.; Keller‐Schierlein, W.; Kradolfer, F; Manukian, B. K.; Neipp, L.; Prelog, V.; Reusser, P; Zähner, Hans

doi:10.1002/hlca.19570400518

Cited by 64 publications

(30 citation statements)

References 9 publications

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“…The results of the FD-mass spectrum and elemental analysis suggest that the mederrhodin A molecule contains a hydroxyl residue in addition to the medermycin molecule. UV absorptions of mederrhodins A and B were different from those of medermycin and were quite similar to those of actinorhodin (2) and granaticin (19). This suggests that the chromophores of mederrhodins A and B were derived from naphthazarin (2).…”

Section: Resultsmentioning

confidence: 89%

Production of new hybrid antibiotics, mederrhodins A and B, by a genetically engineered strain

Ōmura¹,

Ikeda²,

Malpartida³

et al. 1986

Antimicrob Agents Chemother

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Hybrid antibiotics mederrhodins A and B were produced by a recombinant strain consisting of the medermycin-producing Streptomyces sp. strain AM7161 containing part of the gene clusters for actinorhodin biosynthesis of Streptomyces coelicolor A3(2). Mederrhodin A has a hydroxyl group at the C-6 position of the medermycin molecule, and mederrhodin B is dihydromederrhodin A. The antimicrobial activity of mederrhodin A resembled that of medermycin. Mederrhodin B was almost devoid of antimicrobial activity.

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Section: Resultsmentioning

confidence: 89%

Production of new hybrid antibiotics, mederrhodins A and B, by a genetically engineered strain

Ōmura¹,

Ikeda²,

Malpartida³

et al. 1986

Antimicrob Agents Chemother

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“…32). This was established by following the time course of the appearance of the two compounds in the f e r m e n t a t i~n~~~.~'~ and by observing unidirectional conversion of 54 to 19 in cerulenin-inhibited and in cell-free extracts of S. uiofaceoruber.1611 Consistent with the mechanism shown in Figure 33, the enzymatic reaction is dependent on oxygen but no "0 is incorporated into the product when the conversion is carried out in an atmosphere of I8O2 gas. parallels that seen in the nanaomycin series (50 + 51 + 60 -+ 53, Fig.…”

Section: Biosynthetic Interrelations Among Benzoisochromane Quinone Amentioning

confidence: 99%

Biosynthetic Studies on Antibiotics

Floss

Beale

1989

Angew. Chem. Int. Ed. Engl.

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The intricacies of the synthetic chemistry executed by living cells in the assembly of complex organic natural products can be probed in great detail by stable-isotope labeling in conjunction with sophisticated 2D and multiple-quantum NMR methods of analysis. Mechanistic details are revealed by unraveling the "cryptic" stereochemistry of biosynthetic reactions with the aid of stereospecific isotope labeling. Analysis of blocked mutants and cloning of biosynthetic genes provides new tools for the study of biosynthetic pathways and for the exploitation of the chemical capabilities of living organisms.

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“…The feasibility of this approach was first demonstrated in work by David Hopwood and colleagues (Hopwood et al, 1985). Following the cloning of the biosynthetic genes for the antibiotic actinorhodin from Streptomyces coelicolor (Malpartida & Hopwood, 1984), Hopwood and coworkers cloned some or all of these genes into the producers of the antibiotics medermycin (Takano et al, 1976) and dihydrogranaticin (Corbaz et al, 1957), respectively. The transformant of the medermycin producer, Streptomyces sp.…”

Section: Introductionmentioning

confidence: 99%

Combinatorial biosynthesis—Potential and problems

Floss

2006

Journal of Biotechnology

139

114

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Because of their ecological functions, natural products have been optimized in evolution for interaction with biological systems and receptors. However, they have not necessarily been optimized for other desirable drug properties and thus can often be improved by structural modification. Using examples from the literature, this paper reviews the opportunities for increasing structural diversity among natural products by combinatorial biosynthesis, i.e., the genetic manipulation of biosynthetic pathways. It distinguishes between combinatorial biosynthesis in a narrower sense to generate libraries of modified structures, and metabolic engineering for the targeted formation of specific structural analogs. Some of the problems and limitations encountered with these approaches are also discussed. Work from the author's laboratory on ansamycin antibiotics is presented which illustrates some of the opportunities and limitations. KeywordsCombinatorial biosynthesis; metabolic engineering; natural products; rifamycin; maytansinoids; polyketides Combinatorial biosynthesis can be defined as the application of genetic engineering to modify biosynthetic pathways to natural products in order to produce new and altered structures using nature's biosynthetic machinery. The feasibility of this approach was first demonstrated in work by David Hopwood and colleagues (Hopwood et al., 1985). Following the cloning of the biosynthetic genes for the antibiotic actinorhodin from Streptomyces coelicolor (Malpartida & Hopwood, 1984), Hopwood and coworkers cloned some or all of these genes into the producers of the antibiotics medermycin (Takano et al., 1976) and dihydrogranaticin (Corbaz et al., 1957), respectively. The transformant of the medermycin producer, Streptomyces sp. AM-7161 produced, in addition to medermycin, large amounts of a new compound, mederrhodin A, which carried an additional hydroxy group characteristic of actinorhodin ( Figure 1). The transformant of the dihydrogranaticin producer, Streptomyces violaceoruber Tü 22 produced a new compound, dihydrogranatirhodin, which has the actinorhodin configuration at one and the dihydrogranaticin configuration at the other stereocenter of the isochromane quinone system. This work represents the first, albeit modest, implementation of the concept of combinatorial biosynthesis of natural products. Since then, a large number of examples encompassing a wide range of natural product classes have appeared in the literature, and this approach has been accepted as a useful tool to increase the chemical diversity of natural products (Staunton and Wilkinson, 2001;Walsh, 2002;Rix et al., 2002;Reeves, 2003). Following the author's primary interests, this article focuses on the application of the combinatorial biosynthesis approach to microbial natural products and within these to Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript ...

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Stoffwechselprodukte von Actinomyceten. 9. Mitteilung. Granaticin

Cited by 64 publications

References 9 publications

Production of new hybrid antibiotics, mederrhodins A and B, by a genetically engineered strain

Production of new hybrid antibiotics, mederrhodins A and B, by a genetically engineered strain

Biosynthetic Studies on Antibiotics

Combinatorial biosynthesis—Potential and problems

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