Neomycin biosynthetic pathway

Ribose is formed by a different pathway or pathways and evidence indicates major participation of a C-6 oxidative route, presumably the glucuronic acid path. Much remains to be done. The precise nature of the immediate precursor to the neosamines and deoxystreptamine is not estabhshed, nor is the presence of a symmetrical intermediate certain. The order of formation of the glycosidic bonds is still to be demonstrated. The apphcabihty of the neomycin biosynthetic pathway to other, related antibiotics is of interest. Finally, the relationship of neomycin biosynthesis to the primary metaboHsm of Streptomyces fradiae is uncertain, though the imphcation of UDP-N-acetylglucosamine in neomycin synthesis imphes some intermediates in common with cell wall synthesis. 

More frequently, however, mutation is used to block a particular pathway. Streptomyces fradiae produces neomycin. 2-Deoxystreptamine is an intermediate in the biosynthetic pathway leading to the production of neomycin (see Figure 6.20). 

A mutant strain of Micromonospora purpurea synthesized gentamicin antibiotics on being fed with the inososes (505) and (506), which are presumably converted into streptamine and 2-deoxystreptamine, respectively, prior to incorporation into the intact antibiotics. A mutant strain of S.fradiae synthesized the pseudotrisaccharide ribostamycin (see Vol. 10, p. 131) instead of the pseudotetrasaccharide neomycin. After a second and reverse mutation, new colonies again synthesized neomycin, indicating that ribostamycin may be an intermediate along the biosynthetic pathway leading to neomycin. A chemical synthesis of neomycin C (507) from a derivative of ribostamycin is shown in Scheme 85. ... 

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