Streptidine biosynthesis

The General myo-lnositol and scyllo-Inosamine Pathway. Two distinct cyclitol pathways, which we earlier called Ca (started by myo-inositolphos-phate synthase) and Cb (started by T-deoxy-i cy/to-inosose synthase), are used in the initiation of AGA pathways. Here we will describe the Ca route and the Cb pathway in the paragraph on NEOs (see Section 2.2.2.1.3). The cyclitol pathway in the biosynthetic pathways for STRs, but also for other AGAs such as SPCs, KAS, and FORs and also the mixed type antibiotic HYG-A (see Section 2.2.4.3.1), starts with the formation of myo-inositol in a two-step pathway (Ca) that is not encoded in the itrAtt-clusters. The first step in streptidine biosynthesis (and any other myo-inositol utilising pathway) is the formation of a myo-inositol monophosphate (D-myo-inositol-3-phosphate or L-myo-inositol-1-phosphate) via L-myo-inositol-1-phosphate synthase, which in actinomycetes... 

Not much has been added to the biochemistry of STRs in the recent years. Therefore, we will only briefly treat the biosynthetic pathway here. Biosynthesis of the aminocyclitol (streptidine) and 6-deoxyhexose (streptose) moieties are well understood, with some remaining gaps in the enzymology. Much less is known about the residual biosynthetic phases, the formation of A-methyl-L-glucosamine, the condensation of subunits, and the late modification steps potentially coupled with export. ... 

Loss of tritium from D-glucose-3-t (but not from D-glucose-J-f) during the biosynthesis of L-streptidine (77), which is a component of the antibiotic streptomycin, showed that the 3-guanidination of D-l-deoxy-l-guanidino-sci/Wo-inositol (75) may proceed through the 3-ketone intermediate 76. The enzyme system was specific195 for the D-isomer (75). 

The biosynthesis of the dihydrostreptose moiety has already been described. The biosynthesis of the streptidine and 2-deoxy-2-(methyl-amino)-L-glucose moieties, and their assembling to give the antibiotic, will now be discussed. Furthermore, the biosynthesis of the bluensi-dine moiety of bluensomycin will be compared with that of streptidine. 

From these results, it may be concluded that the pseudo-disaccharide 44 is the first intermediate in the assembling of the three components of dihydrostreptomycin. The fact that no transfer-product was observed with streptidine is in agreement with the conclusions from a number of studies in which the importance of phosphorylated intermediates in the biosynthesis of streptomycin was established.36,64,65... 

S ATP -I- scjZZo-inosamine <1> (<1> reaction involved in biosynthesis of streptidine from myo-inositol [1]) [1]... 

Walker, J.B. Walker, M.S. Streptomycin biosynthesis. Enzymatic synthesis of 0-phosphorylstreptidine from streptidine and adenosinetriphosphate. Bio-chim. Biophys. Acta, 148, 335-341 (1967)... 

In addition to streptomycin biosynthesis the A-factor influences strongly the formation of a number of related compounds. So, zero mutants do not produce streptidine or phosphostreptidlne in A-factor absence, but produce them in its presence. Simultaneously in the presence of the A-factor the activity of naae... 

Bioconversions of aminoglycoside antibiotics have been discussed. Further studies in the biosynthesis of streptomycin have shown that only streptidine-6-phosphate acts as an acceptor for dihydrostreptose in the synthesis of O-a-L-dihydrostreptose(l ->-4)streptidine-6-phosphate using a purified enzyme preparation from S. griseus, and that this pseudodisaccharide could be... 

Kniep B, Grisebach H. Biosynthesis of stieptomycin. Purification and propenies of a dTDP-L dihvdro5treptose streptidine 6-phosphate dihydrostreptosyltransferase from Sirepiomyces griseus. EurJ Biochem 1980 105 139-144. 

Isotopic labelling with D-[6- C]glucose has established that C-6 of streptidine is derived from C-6, rather than from C-2, of D-glucose in the biosynthesis of streptomycin by Streptomyces griseus. ... 

Bruton, J., W. H. Horner, and G. A. Russ Biosynthesis of streptomycin. IV. Further studies on the biosynthesis of streptidine and N-methyl-L-glucosamine. J. Biol. Chem. 242, 813 (1967). 

Horner, W. H. Biosynthesis of streptomycin II. Myo-inositol, a precursor of the streptidine moiety. J. Biol. Chem. 239, 2256 (1964b). 

Walker, M. S., and J. B. Walker Evidence for participation of a phosphorylated derivative of streptidine in streptomycin biosynthesis. Biochim. et Biophys. Acta 97, 397 (1965). 

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