Neomycins biosynthesis

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],... 

Goda SK, Akhtar M. Neomycin biosynthesis The incorporation of D-6-deoxygIucose derivatives and variously labelled glucose into the 2-deoxystreptamine ring. Postulated involve ment of Z deoxyinosose synthase in the biosynthesis. J Antibiot 1992 45 984-994. 

The meaning of this latter observation is not clear. If one ignores the result at higher nucleotide level, then UDP-NAG may be reasonably regarded as an intermediate in neomycin biosynthesis. It is probable that it is also an intermediate in S. fradiae cell wall biosynthesis since it is known to be an intermediate in other cell wall syntheses (Strominger, 1962) and the cell walls of S. fradiae contain an inordinately large amount of glucosamine (Sohler, Romano and Nickerson, 1958). 

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. 

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. 

Waksman et al, in 1949, first reported the production of neomycin by fermentation of a culture of S. faUcid-Lcut. (3535). The same organism subsequently formed the basis of an industrial fermentation process for the biosynthesis of neomycin287,288. isolation of the antibiotic from the fermentation media is accomplished by use of ion-exchange resins, such as Amberlite IRC 50 25,250,251. 

The biosynthesis of neomycin (see Scheme 17) has been studied by Rinehart and coworkers.53 Early incorporation studies with D-[l-... 

Scheme 12. 5-Deoxygenation during the biosynthesis of 2-deoxystreptamine (27 the core moiety of neomycin 25, streptamine 26 is its analog in streptomycin 24) through transamination of the intermediate 2-deoxy-scyl/o-inosose (28). Note that C-5 of glucose becomes C-3 of 26 and 27...

The biosynthesis of paromomycin, ribostamycin, butirosin, kanamycin and siso-micin proceeds in a manner similar to that of neomycin from deoxystreptamine, but it differs in some details ... 

C] Glucose has been employed in work on the biosynthesis of streptomycin [221] and neomycin [222], while the incorporation of [l- C]glucos-amine into neomycin has also been studied [222]. 

Suppression by excess nutrients has been found in the biosynthesis of polyketides (D 3.3), of gibberellins (D 6.3), of certain antibiotics, e.g., streptomycin (D 1.3), neomycin C (D 1.3), actinomycins (D 8.4.1), chloramphenicol (D 8.2), bacitracin A (D 23), enniatin B (D 23), cephalosporins (D 23.3), and penicillins (D 23.3), of alkaloids, e.g., benzodiazepines (D 8.4.2), and ergolines (D 21.2) etc. Usually the suppression of secondary product formation is accompanied by the suppression of other characteristics of cell specialization (such as conidiospore formation in Peni-cillium cyclopium), indicating a general influence of nutrient supply on cell specialization. 

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