None of these components has been found in the primary metabolism of microorganisms. The biosynthesis of streptomycin was disclosed mainly by Walker [12], who also studied the enzymes participating in the biosynthesis of streptomycin.
The importance of streptomycin consists mainly in its efficiency to suppress Mycobacterium tuberculosis. A massive use of streptomycin resulted in effective suppression of tuberculosis, especially in developed countries. Recently, however, the disease caused by M. tuberculosis has been found to increase again due to the occurrence of strains resistant to streptomycin.
Antiviral compounds. Recently also compouds active against viruses have been discovered. Sattabacins and sattazolins, isolated from Bacillus sp. and fattivirin A1, isolated from Streptomyces microflavus are active against Herpes simplex viruses. Inhibitors of HIV are intensively looked out in microorganisms. Inhibitors of HIV - 1 protease were detected in fungus Chrysosporium merdarium P - 5626. A compound which has an inhibitory effect on HIV - 1 replication in chronically infected cells as well as actualy infected cells was isolated (after screeninng 10,000 microorganism products) from the culture supernatant of Streptomyces sp. Mer - 2487. A hydroxyl benzaldehyde compound, active against influenza virus in vitro, was isolated from Aspergillus terreus. Rhodopseudomonas capsulata produces a virucide substance which inactivated polio virus, Sindbis virus, some fish viruses, without causing any damage to the host cells.
1.1.3 Genetics production strains.The genes coding the enzymes that synthesize antibiotics are mostly located on chromosomes. These genes are called structural genes and the enzymes taking part in the antibiotic synthesis are called the enzymes of secondary metabolism. The structural genes are organized to form one cluster. This situation has been observed in all cases described so far. The expression of structural genes is controlled in a similar way as in the case of other genes. Next to a cluster of the structural genes, the genes coding for the resistance of the producer to its own antibiotic are located. Those genes are situated either at the beginning or at the end of the cluster, often in both positions. In the case the resistance genes are present in the two positions, different types of resistance are included as a rule. In addition to the structural genes, regulation genes also determine the antibiotic production. They are often located on plasmids. The genetic control of antibiotic biosynthesis is poorly known. The type of control where the antibiotic synthesis is inhibited by the own product can serve as an example. As a result, the product s cellular concentration is maintained at a physiologically tolerable level and, consequently, the producing microorganism is prevented from being self damaged by high concentrations of the product, that are toxic.
Multiplication of the structural genes is not an important factor increasing the antibiotic production. Mutations resulting in an increased antibiotic synthesis mostly affect the regulatory genes. Hopwood and co-workers [12-13] transferred the genes for the production of actinorhodine to a low production, wild type strain using a plasmid. Even though the number of copies of the structural gene increased only twofold, the production of the antibiotic rose 30-40 times. The increase of the antibiotic production has to be accompanied by an increase of resistance to the own product.
When high production strains are prepared by mutagenesis, a type of mutant that loses some of the structural genes can also be obtained. Such a mutant can exhibit a higher level of an antibiotic intermediate whose transformation stopped due to the absence of the corresponding enzyme. By crossing these mutants, some biosynthetic pathways used to synthesize antibiotics were elucidated, eg tetracyclines. Genetic manipulation of antibiotic producers. The structural genes for a number of antibiotics have been cloned into host microorganisms. Similarly, genes for antibiotic resistance and other regulatory genes have also been cloned. Streptomyces lividans was found to be a suitable acceptor of foreign genetic material, in which a low degree of restriction of this genetic material exists. This microorganism can host various plasmids and phage vectors. However, at the same time, this microorganism was found not to be usable for the synthesis of various antibiotics or of high antibiotic levels. The antibiotic biosynthesis is a very complex process that requires not only the structural genes for enzymes of secondary metabolism but also the genes for regulation of their biosynthesis. Moreover, the overproduction of an antibiotic has to be coordinated with the primary me...
