NEW NIKKOMYCINS BY MUTASYNTHESIS AND DIRECTED FERMENTATION

The nikkomycins, nucleoside peptide antibiotics, produced by Streptomyces tendae inhibit the chitin syntheses of fungi and insects. Uracil and 4-formyl-4-imidazoline-2-one are the variable bases of the natural nikkomycins. Since uracil originates from the pyrimidine metabolism, pyr mutants, which ar...

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Bibliographic Details
Published in:Journal of antibiotics 1984, Vol.37(1), pp.80-82
Main Authors: DELZER, JÜRGEN, FIEDLER, HANS-PETER, MÜLLER, HARTWIG, ZÄHNER, HANS, RATHMANN, RALPH, ERNST, KARIN, KÖNIG, WILFRIED A.
Format: Article
Language:English
Subjects:
Aminoglycosides
Anti-Bacterial Agents
Antibiotics
Antibiotics (antibacterial agents, antifungal agents)
Antibiotics, microbial producers, chemotherapic agents, antiseptics, disinfecting agents
Antifungal Agents - biosynthesis
Applied microbiology
Biological and medical sciences
Biotechnology
Chitin Synthase - metabolism
Fermentation
Fundamental and applied biological sciences. Psychology
Health. Pharmaceutical industry
Industrial applications and implications. Economical aspects
Microbiology
mutants
nikkomycin
Nucleosides - biosynthesis
peptide antibiotics
Production of active biomolecules
Streptomyces - metabolism
Streptomyces tendae
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Summary:The nikkomycins, nucleoside peptide antibiotics, produced by Streptomyces tendae inhibit the chitin syntheses of fungi and insects. Uracil and 4-formyl-4-imidazoline-2-one are the variable bases of the natural nikkomycins. Since uracil originates from the pyrimidine metabolism, pyr mutants, which are not able to form uracil, produce only nikkomycins with the 4-formyl-4-imidazoline-2-one base. Twenty-three N-heterocyclic compounds, including pyrimidines, purines and imidazoles, were fed to the nikkomycin producer (directed fermentation) and to the pyr mutants descended from it (mutasynthesis). Upon administration of the three pyrimidine - thymine, 5-hydroxymethyluracil and 5-formyluracil - interesting additional peaks were detected in the HPLC. To qualify as new nikkomycins the peaks must have certain characteristics: pH stability and binding to cation and anion exchange resins. Furthermore, the sequence of the nikkomycins in the HPLC corresponds to that of their bases, and from one base both nikkomycin Z- and J-analogues are produced. Isoorotic acid, another base, did not show any new peaks; instead, production of nikkomycins Z and J was increased. The combination of high voltage electrophoresis with various biological tests and HPLC analysis showed that a new weakly active nikkomycin was produced.
ISSN:0021-8820
1881-1469
DOI:10.7164/antibiotics.37.80