Aminoglycoside antibiotics biosynthesis

Aminoglycosides. Antibiotics ia the amiaoglycoside group characteristically contain amino sugars and deoxystreptamiae or streptamiae. This family of antibiotics has frequentiy been referred to as aminocyclitol amiaoglycosides. Representative members are streptomycia, neomycin, kanamycia, gentamicin, tobramycia, and amikacin. These antibiotics all inhibit proteia biosynthesis. 

Piepersberg, W. Streptomycin and related aminoglycosides. In Biochemistry and Genetics of Antibiotic Biosynthesis Vining, L. Stuttard, C., Eds. Boston Butterworth-Heinemann, 1995 pp. 531-570. 

Okuda, T. Ito, Y. Biosynthesis and mutasynthesis of aminoglycoside antibiotics. In Aminoglycoside Antibiotics Umezawa, H. Hooper IR., Eds. Berlin Springer-Verlag, 1982 pp. 111-203. 

Piepersberg W, Streptomycin and related aminoglycosides In Vining LC, Stut-tard C (eds.), Biochemistry and Genetics of Antibiotic Biosynthesis Butterworths-Heinemann, Boston, MA, pp. 531—570, 1999. 

Inhibition of protein synthesis by aminoglycoside antibiotics, especially by streptomycin, is bactericidal (rev.46)). The antibiotic binds to the smaller ribosomal subunit and leads to the formation of abortive initiation complexes of ribosomes, streptomycin and amino acyl tRNA which progressively trap ribosomes in the form of such biologically irreversible complexes. When protein synthesis is prematurely terminated by puromycin and ribosomes are thus made available for reinitiation of de novo protein biosynthesis, the bactericidal action of streptomycin is accelerated47). Destruction of ribosomes under the influence of primaquine operationally also results in non-occurrence of protein synthesis and in a marked bactericidal effect48, 49 ... 

Instead of describing the biosynthesis of the individual sugar components of these antibiotics, it is advantageous to review the biosynthesis of the total molecule. A review on the biosynthesis of aminocyclitol ( aminoglycoside ) antibiotics has appeared.47... 

Reviews by Hanessian et al. [20], Umezawa [21], and Cox et al. [22] deal with the chemistry of aminoglycosides Price [23] has reviewed structure-activity relationships, and Umezawa et al. [24,25] have discussed the structure, synthesis, and biosynthesis of aminoglycoside antibiotics. This chapter summarizes what is known of the stmctural classes of aminoglycosides to date and presents state-of-the-art knowledge of the mechaiusms for manifestation of the biological activities of these versatile antimicrobials. 

Some mutants have been used during biosynthesis to incorporate modified deoxystreptamine derivatives. In such so called mutasynthesis or mutational biosynthesis new aminoglycoside antibiotics can be prepared. A series of analogues of 2-deoxystreptamine has been used in different 2-deoxystreptamine-negative mutants to determine whether they are converted to antibiotics. Only limited substitution at the 2-position (streptamine, epi-streptamine, 1-N-methyldeoxystrepta-... 

Aminoglycoside antibiotics inhibit the protein biosynthesis in sensitive organisms. The reaction takes place at the ribosomes. (Reviews see Refs. The... 

Bioconversions of aminoglycoside antibiotics have been discussed. Further studies in the biosynthesis of streptomycin have shown that only streptidine-6-phosphate acts as an acceptor for dihydrostreptose in the synthesis of O-a-L-dihydrostreptose(l ->-4)streptidine-6-phosphate using a purified enzyme preparation from S. griseus, and that this pseudodisaccharide could be... 

Hotia K. Davies J, Ya sawa M. Aminoglycosides and ammocycliiols (other than strepto mycin). Vining L, Stuttard C, eds. Biochemisrry and Genetics of Antibiotic Biosynthesis Sroneham Butterwonh-Heinemann, 1994 571-595. 

The pathways for biosynthesis of the unusual sugars found in glycopeptide antihi-otics have not been studied. However, it would be expected that there will be considerable overlap with the aminosugar biosynthesis occurring in the tnacrolide and aminoglycoside antibiotics. 

The biosynthesis of the aminoglycoside antibiotics has been reviewed. Apramycin, a broad-spectrum aminoglycoside antibiotic produced by a strain of Streptomyces tenebrarius, has been assigned the structure (361), which contains residues of 4-amino-4-deoxy-D-glucose and an octadiose that exists as a rigid bicyclic system. The structure (361), which was first derived from chemical and spectroscopic evidence, was confirmed by A"-ray crystallographic analysis. 

The biosynthesis of sagamicin and related aminoglycoside antibiotics has been studied using blocked mutants of... 

The medically useful products demethyltetracycline and doxorubicin (adriamycin) were discovered by simple mutation of the cultures producing tetracycline and daunorubicin (daunomycin), respectively. The tectmique of mutational biosynthesis (mutasynthesis) has been used for the discovery of many new aminoglycoside, macrolide, and anthracycline antibiotics. In this tectmique, a non-producing mutant ( idiotroph ) is isolated and then fed various analogs of the missing moiety. When such a procedure leads to a return of antibiotic activity, it usually is due to the... 

Kase, H. Odakura, Y. Takazawa, Y. Kitamura, S. Nakayama, K. Biosynthesis of sagamicin and related aminoglycosides. In Trends in Antibiotic Research. Genetics Biosyntheses, Actions, and New Substances Umezawa, H. Demain, A. L. Hata,... 

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