Biosynthesis of Aminoglycoside Antibiotics

Abstract

Aminoglycoside antibiotics are pseudo-oligosaccharides that have a cyclitol core attached to a small number of amino sugars. Streptomycin, neomycin, and kanamycin are representative aminoglycoside antibiotics. Formation of the core cyclitol, glycosylation of the cyclitol, and introduction of the amino group into the sugar moieties are common biosynthetic reactions. Modification of the cyclitol and sugar moieties, including via C-methylation, N-methylation, epimerization, and deoxygenation, can expand the structural diversity of aminoglycoside antibiotics. In this book chapter, the biosynthetic reaction mechanisms that are involved in the biosynthesis of aminoglycoside antibiotics are classified into common reaction types. First, cyclitol formation from d-glucose 6-phosphate is described. Next, enzymatic reactions to construct common oligosaccharide structures using glycosyltransferases, deacetylases, dehydrogenases, and aminotransferases are described. Then, modification reactions, including C-methylation, N-methylation, epimerization, deoxygenation, and aminoacylation are described. The biosynthetic pathways for glycosyl donors in the biosynthesis of aminoglycoside antibiotics are also described.