Detection and Expression of Biosynthetic Genes in Actinobacteria ...

BERVANAKIS, G.Chapter 1: INTRODUCTION1.3.2 Biosynthesis of Deoxysugar Aminoglycoside AntibioticsAminoglycoside (AG) antibiotics are compounds which contain aminosugars andoften an aminocyclitol ring (Table 4). They are broad spectrum antibiotics, effectiveagainst both Gram positive and Gram negative bacteria (Liu & Thorson, 1994).Deoxysugar components are usually attached to specific positions on theaminocyclitol ring and serve to modulate biological functions. Deoxysugars aredefined as carbohydrates in which one or more of the normally (e.g., glucose)occurring oxygen atoms are deleted (i.e., replaced by hydrogen, thiosugars, halogens,aminosugars or nitrososugars). The biosynthesis of 6-deoxysugar AG antibiotics hasnot been well defined with segments of the biosynthetic pathway only beginning tobe characterised (Johnson and Liu, 1998). Figure 10B shows the biosynthetic pathwayof the 6-deoxyhexose containing AG streptomycin. The first step involves theconversion of glucose-1-phosphate into dTDP-D-glucose by the action of dTDPglucosesynthase. The next catalytic step involves dTDP-D-glucose 4,6 dehydratasewhich converts dTDP-D-glucose into dTDP-D-4-keto-6-deoxyglucose [Figure 10B;step 2]. Further catalysis by 5- or a 3,5 epimerase directs dTDP-D-4-keto-6-deoxyglucose into D or L series of 6-deoxyhexoses [Figure 10B; step 3]. Subsequentmodifications can be achieved by further deoxygenations, O-methylations,transaminations or reduction (Johnson & Liu, 1999).Table 4. Aminoglycoside antibiotics produced by actinobacteria.Chemical StructureName of Biological Activitiescompound/ProduceraminocyclitolStreptomycinStreptomycin griseusAntibacterialdeoxysugaraminocyclitolNeomycinStreptomyces fradiaeAntibacterialdeoxysugar_____________________________________________________________________19