Aminoglycosides biosynthesis

Aminoglycoside Biosynthesis. The biosynthesis of the aminoglycosides has been extensively studied and reviewed (117—119). Perhaps the most interesting aspect is the biosynthesis of 2-deoxystreptamiae (1, R = H), in which the C-1 and C-6 of a D-glucose molecule become the C-1 and C-2 of 2-deoxystreptamiae by way of the intermediate 2-deoxy-j //(9-iaosose. The details of this conversion are stiU unclear. 

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. 

Aminoglycosides Tetracyclines Chloramphenicol Erythromycin Clindamycin Spectinomycin Mupirodn Fusldfc add Inhibition of protein biosynthesis... 

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... 

Piepersberg, W. Diaz-Guardamino, P. M. Zhang, C. S. Stratmann, A. Wehmeier, U. F. Recent advances in biosynthesis and regulation of aminoglycosides. In Microbial Secondary Metabolites, Fierro, F. Martin, J. F. Eds. Kerala, India Research Signpost, 2002 pp. 1-26. 

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. 

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,... 

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. 

As a group, the protein biosynthesis inhibitors comprise the second largest class of antibiotics available for clinical use. Natural product classes of antibiotics that inhibit the protein biosynthesis are aminoglycosides, tetracyclines, chloramphenicol, macrolides, lincosamides, fusidic acid, streptogramins and mupirocin (Fig. 7). 

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... 

From these examples it is clear that nature also provides convergent alternatives to the linear assembly of deoxysaccharides, as was, for example, observed in tylosin [90] or streptomycin (24) biosynthesis [72], A linear strategy is certainly also true for other aminoglycosides, although in the case of neomycin biosynthesis, an alternative disaccharyl transfer has been discussed [70],... 

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