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Biosynthesis of Other Classes of Antibiotics, Page 1 of 2
< Previous page Next page > /docserver/preview/fulltext/10.1128/9781555817886/9781555818937_Chap14-1.gif /docserver/preview/fulltext/10.1128/9781555817886/9781555818937_Chap14-2.gifAbstract:
This chapter discusses the enzymatic logic for the formation of certain classes of natural products that have been used in human medicine as antibiotics. The aminoglycoside, or aminocyclitol, antibiotics represent products of secondary carbohydrate metabolism and are prevalent among actinomycetes. Starting with the isolation of streptomycin in 1944, various family members were discovered over the following 25 years, including tobramycin in 1970. Novel aminocyclitols continued to be reported into the 1990s. Two main categories of these carbohydrate antibiotics are exemplified by the streptomycin class and by the 2-deoxystreptamine-containing antibiotics that include neomycins, kanamycins, and gentamicins. The glycoside-to-cyclitol conversion, central to streptomycin antibiotic biosynthetic pathway logic, is found in primary metabolism for the generation of inositol-phosphate from glucose-6- phosphate (glucose-6-P) on the way to phosphoinositide membrane lipid biosynthesis. The prospects for combinatorial biosynthesis to make new aminocyclitols, e.g., with more rings and new connectivities, may be good, setting up the systems for new rounds of semisynthetic alkylations and acylations, although it remains to be seen if useful new activities will result. The bicyclic aminocoumarin ring is constructed from tyrosine, in turn derived from chorismate, the key intermediate in aromatic amino acid biosynthesis. Some of the logic and mechanism of nonribosomal peptide synthetase selection, activation, and modification of amino acid monomers is utilized in these amino acid-based antibiotics.