This review aims at comparing some historical data with the current situation in the study of biogenesis of natural compounds, antibiotics in the first place. Biogenesis of tetracyclines and cycloheximide and related compounds serves as example. Examples of molecular biological and bioinformatics methods used in the study of antibiotic biogenesis are described both in terms of its historical aspects and the current knowledge.

• MeSH
• Anti-Bacterial Agents biosynthesis   metabolism   MeSH
• History, 20th Century MeSH
• History, 21st Century MeSH
• Metabolic Networks and Pathways genetics   MeSH
• Drug Discovery history   MeSH
• Computational Biology MeSH
• Check Tag
• History, 20th Century MeSH
• History, 21st Century MeSH
• Publication type
• Journal Article MeSH
• Historical Article MeSH
• Review MeSH
• Names of Substances
• Anti-Bacterial Agents MeSH

Using the examples of biosynthesis of streptomycin, bialaphos, actinorhodin, oligoketides and autoregulators during the first hours of streptomycete cultivation, it is stressed that the external environment in cooperation with the internal metabolic abilities of the cell determines the metabolic type that would develop during the life cycle of the producing streptomycetes. If we accept that a certain metabolic type (from the point of view of the production of secondary metabolites) was determined already during the first hours of cultivation of the microorganisms, we must also admit that the availability of primary metabolites in the so-called production phase of growth (stationary phase, idiophase, etc.) is to a certain extent determined by the very early stages of strain development.

• MeSH
• Anthraquinones metabolism   MeSH
• Anti-Bacterial Agents biosynthesis   MeSH
• Time Factors MeSH
• Organophosphorus Compounds metabolism   MeSH
• Gene Expression Regulation, Bacterial MeSH
• Streptomyces physiology   MeSH
• Streptomycin biosynthesis   MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Review MeSH
• Names of Substances
• actinorhodin MeSH Browser
• Anthraquinones MeSH
• Anti-Bacterial Agents MeSH
• bialaphos MeSH Browser
• Organophosphorus Compounds MeSH
• Streptomycin MeSH

Substances studied at this department in 1954-1983 are reviewed; a total of 226 compounds are characterized in a tabular form. They include natural compounds as well as those prepared by biotransformation, by semisynthetic and synthetic methods.

• MeSH
• Anti-Bacterial Agents isolation & purification   MeSH
• Microbiology MeSH
• Chemistry, Organic * MeSH
• Organic Chemistry Phenomena MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Anti-Bacterial Agents MeSH

A new metabolite denoted as verotetrone was isolated from the mycelium of the mutant strain Streptomyces aureofaciens NMG-2. Interpretations of physical data concerning verotetrone and its triacetate and, the determination of its degradation product indicate that verotetrone belongs to pretetramide-type metabolites. Verotetrone exhibits neither antibacterial nor antifungal activity. In vitro it inhibits the synthesis of nucleic acids as well as proteins in Ehrlich ascites carcinoma cells. Both verotetrone and its triacetate interfere in vivo with the metabolism of tumour and lymphoid cells, exhibiting antitumour or immunosuppressive activity. This activity, which is more intense with verotetrone than with its triacetate, is detectable in a dose which is already toxic in some animals.

• MeSH
• Anthracyclines * MeSH
• Bacteria drug effects   MeSH
• Candida drug effects   MeSH
• Carcinoma, Ehrlich Tumor metabolism   MeSH
• Leukemia, Experimental drug therapy   immunology   MeSH
• Neoplasms, Experimental MeSH
• Mice, Inbred Strains MeSH
• Mutation MeSH
• Mice MeSH
• Naphthacenes analysis   isolation & purification   pharmacology   MeSH
• Nucleic Acids biosynthesis   MeSH
• Antibiotics, Antineoplastic * MeSH
• Streptomyces aureofaciens metabolism   MeSH
• Transplantation Immunology MeSH
• Animals MeSH
• Check Tag
• Mice MeSH
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Anthracyclines * MeSH
• Naphthacenes MeSH
• Nucleic Acids MeSH
• Antibiotics, Antineoplastic * MeSH
• verotetrone MeSH Browser

• MeSH
• Anti-Bacterial Agents biosynthesis   MeSH
• Bacteria growth & development   metabolism   MeSH
• Bacterial Proteins metabolism   MeSH
• RNA, Bacterial metabolism   MeSH
• DNA, Bacterial metabolism   MeSH
• DNA metabolism   MeSH
• Fungi growth & development   metabolism   MeSH
• RNA metabolism   MeSH
• Spores, Bacterial physiology   MeSH
• Streptomyces growth & development   metabolism   MeSH
• Publication type
• Journal Article MeSH
• Review MeSH
• Names of Substances
• Anti-Bacterial Agents MeSH
• Bacterial Proteins MeSH
• RNA, Bacterial MeSH
• DNA, Bacterial MeSH
• DNA MeSH
• RNA MeSH

The production of epsilon-pyrromycinone glycosides in Streptomyces galilaeus increased 12-fold, with respect to the wild strain, as a result of a sequential procedure including both natural selection and treatment with mutagens (nitrous acid, UV light and gamma-irradiation). Nitrous acid exhibited the highest mutagenic effect, both in increasing the productivity and in inducing blocked mutants. A mutant strain blocked in the biosynthesis of glycosides and accumulating free epsilon-pyrromycinone as the principal metabolite was obtained.

• MeSH
• Anthraquinones biosynthesis   MeSH
• Glycosides biosynthesis   MeSH
• Nitrous Acid pharmacology   MeSH
• Mutation drug effects   radiation effects   MeSH
• Antibiotics, Antineoplastic biosynthesis   MeSH
• Streptomyces drug effects   genetics   metabolism   radiation effects   MeSH
• Ultraviolet Rays MeSH
• Gamma Rays MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Anthraquinones MeSH
• Glycosides MeSH
• Nitrous Acid MeSH
• Antibiotics, Antineoplastic MeSH

• MeSH
• Anthraquinones metabolism   MeSH
• Time Factors MeSH
• Chromatography, Thin Layer MeSH
• Fermentation MeSH
• Glucosides biosynthesis   MeSH
• Glycosides biosynthesis   MeSH
• Hydrogen-Ion Concentration MeSH
• Monosaccharides metabolism   MeSH
• Mutation MeSH
• Oligosaccharides metabolism   MeSH
• Buffers MeSH
• Sucrose metabolism   MeSH
• Spectrophotometry MeSH
• Streptomyces aureofaciens metabolism   MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Anthraquinones MeSH
• Glucosides MeSH
• Glycosides MeSH
• Monosaccharides MeSH
• Oligosaccharides MeSH
• Buffers MeSH
• Sucrose MeSH

• MeSH
• Chromatography, Thin Layer MeSH
• Chromomycins analysis   biosynthesis   MeSH
• Species Specificity MeSH
• Culture Media MeSH
• Plicamycin analysis   biosynthesis   MeSH
• Streptomyces metabolism   MeSH
• Ultraviolet Rays MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Chromomycins MeSH
• Culture Media MeSH
• Plicamycin MeSH

• MeSH
• Acridines MeSH
• Arginine metabolism   MeSH
• Bacteriological Techniques MeSH
• Chlortetracycline biosynthesis   MeSH
• Demeclocycline biosynthesis   MeSH
• Histidine metabolism   MeSH
• Aspartic Acid metabolism   MeSH
• Freeze Drying MeSH
• Methionine metabolism   MeSH
• Mutation * MeSH
• Nitrosoguanidines pharmacology   MeSH
• Streptomyces aureofaciens classification   drug effects   isolation & purification   metabolism   radiation effects   MeSH
• Tetracycline biosynthesis   MeSH
• Ultraviolet Rays MeSH
• Dose-Response Relationship, Radiation MeSH
• Publication type
• Journal Article MeSH
• Comparative Study MeSH
• Names of Substances
• Acridines MeSH
• Arginine MeSH
• Chlortetracycline MeSH
• Demeclocycline MeSH
• Histidine MeSH
• Aspartic Acid MeSH
• Methionine MeSH
• Nitrosoguanidines MeSH
• Tetracycline MeSH