Streptomycin biosynthesis

The A-Factor Signal Relay Leading to Streptomycin Biosynthesis 295... 

The major streptomycin resistance determinant, aphD, encoding streptomycin-6-phosphotransferase is encoded just downstream of strR and cotranscribed with strR by read-through from the AdpA-dependent strR promoter.47 The cotranscription of strR and aphD accounts for the prompt induction of streptomycin resistance by A-factor and achieves a rapid increase in self-resistance just before induction of streptomycin biosynthesis. 

Figure 6 The A-factor signal relay to the streptomycin biosynthesis genes. The streptomycin biosynthesis genes, in a total of 27 genes, including the pathway-specific transcriptional activator strR, are shown. The A-factor signal relay starts with A-factor and is then transmitted to ArpA to AdpA to StrR, and finally to the nine transcriptional units covering the whole gene cluster.

Walker, J.B. Walker, M.S. Streptomycin biosynthesis. Enzymatic synthesis of 0-phosphorylstreptidine from streptidine and adenosinetriphosphate. Bio-chim. Biophys. Acta, 148, 335-341 (1967)... 

Regulators of streptomycin biosynthesis and development of Actinomyces streptomycini, in Se-condary Metabolism and c o olution (M. Luckner,... 

In addition to streptomycin biosynthesis the A-factor influences strongly the formation of a number of related compounds. So, zero mutants do not produce streptidine or phosphostreptidlne in A-factor absence, but produce them in its presence. Simultaneously in the presence of the A-factor the activity of naae... 

In 3 - 4 days of culture development the normal strain has very many such structures, whereas they are practically absent in the zero mutant. However, if the zero mutant grows in the presence of the A-factor, it behaves as the normal strain. A striking feature of zero mutants, when they develop in the presence of the A-factor, is the appearance of specific tubular structures, which are always seen in normal strains in the period of streptomycin biosynthesis and are absent in zero strains growing without the A-factor. These structures seem to be directly connected with antibiotic biosynthesis. Thus, the A-factor is an autoregulator which is necessary for the actinomycete not only to perform some biosynthetic reactions, but also to control cardinal processes of development and differentiation. 

S. A. Pliner, L. A. Shevchenko, E. Ya. Kornitskaya, N. S. Ivkina, I. A. Eapoport, A-Factor, providing Streptomycin Biosynthesis by Mutant Strain Acti-noiyes stregtomyclni. DAN SSSB 177, 232 ( 1967),... 

The introduction of molecular genetics approaches to the study of streptomycin biosynthesis started with cloning resistance genes in the mid 1980s (reviewed in Refs. 3... 

Distler j. Eben A, Mansouh K, Pissowotzki K, Stockmann M. Piepersberg W, Gene cluster for streptomycin biosynthesis in Strepiomyces griseus Nucleotide sequence of three genes and analysis of transcriptional activity. Nucl Acids Res 1987 15 8041-8056. 

Ohnuki T, Imanaka T, Aiba S. Self-cloning in Snvptomyces griseus of an str gene cluster for streptomycin biosynthesis and streptomycin resistance. J Bacieriol 1985 164 85-94. 

Walker JB, Skorvaga M, Streptomycin biosynthesis and metabolism. Phosphate transfer from dibydrostreptomycin 6-phosphate to inosamines, streptamine. and 2-deoxystreptamine. J Biol Chem 1973 248 2435-2440. 

Distlei J, Mansouri K, Piepersberg W. Streptomycin biosynthesis in Sireptomyces grtseus. II. Adjacent genomic location of biosynthetic genes and one of two streptomycin resistance genes. FEMS Microbiol Lett 1985 30 151-154. 

Vujaklija D, Horinouchi S. Beppu T. Detection of an A-factor-responsive protein that binds to the upstream activation sequence of strR, a legulatory gene for streptomycin biosynthesis in Streptomyces griseus. J Bacteriol 1993 175 2652-2661. 

Regulation of Streptomycin Biosynthesis Through the Pathway Specific strR Gene in Streptomyces griseus... 

Nishida H, Ohnishi Y, Beppu T, Horinouchi S (2007) Evolution of gamma-butyrolactone synthases and receptors in Streptomyces. Environ Microbiol 9 1986-1994 Ohnishi Y, Kameyama S, Onaka H, Horinouchi S (1999) The A-factor regulatory cascade leading to streptomycin biosynthesis in Streptomyces griseus identification of a target gene of the A-factor receptor. Mol Microbiol 34 102-111... 

If myo-inosose is an intermediate in the interconversion of these two cychtols by S. griseus it is reasonable to expect that both scy//o-inositol and its 2-keto derivative would stimulate streptomycin production as myo-inositol does. Hunter and Hockenhull (195 5) reported that scy/Zo-inositol when added to S. griseus cultures did not enhance streptomycin production. My(9-inosose-2 partially inhibited production and this inhibition was reversed by administration of scyllo-inositol. On the basis of these findings Hunter (1956) suggested, as one possibility, that myo-inosose inhibits the normal synthesis of streptomycin and that scyZ/o-inositol is required for streptomycin biosynthesis. In another series of experiments (Majumdar and Kutzner, 1962 a) supplementation of culture media with myo-inosose at various concentrations had no detectable effect on strepto-... 

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