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Pathway Description
Streptomycin Biosynthesis
Streptomyces griseus
Metabolic Pathway
Streptomycin, an antibiotic discovered in 1943, belongs to a class of drugs called aminoglycoside antibiotics. It is produced by Streptomyces griseus, a soil residing bacteria, and its role is to inhibit translation by interfering with the growth of the bacteria by inducing prokaryotic ribosomes to misread mRNA. This pathway shows the biosynthesis of streptomycin in a bacterial cell of Streptomyces griseus originating from a D-glucose compound. There are three branches to this pathway that give rise to the functional unit monomers: streptidine 6-phosphate, dTDP-L-dihydrostreptose and NDP-N-methyl-L-glucosamine, that streptomycin is made up of. The first branch on the left is involved in the eventual synthesis of the streptidine 6-phosphate intermediate which in this pathway has been shortened to show an intermediate upstream of it: amidino-scyllo-inosamine-4P synthesized via the protein scyllo-inosamine-4-phosphate amidinotransferase. The second branch in the center is involved in the synthesis of the monomer dTDP-L-dihydrostreptose synthesized via the protein putative dTDP-4-dehydrorhamnose 3,5-epimerase. The third branch on the right is involved in the synthesis of the monomer NDP-N-methyl-L-glucosamine from glucose-1-phosphate and no protein is involved in this reaction. The intermediates/monomeric units streptidine 6-phosphate and dTDP-L-dihydrostreptose are then involved in a reaction catalyzed by the protein putative dTDP-dihydrostreptose--streptidine-6-phosphate dihydrostreptosyltransferase to give rise to the intermediate O-(1->4)-alpha-L-dihydrostreptosyl-streptidine 6-phosphate and dTDP. O-(1->4)-alpha-L-dihydrostreptosyl-streptidine 6-phosphate along with NDP-N-methyl-L-glucosamine give rise to dihydrostreptomycin-6P and nucleoside diphosphate. Dihydrostreptomycin-6P reacts to form streptidine 6-phosphate again which reacts in a cyclic manner to form streptomycin. Streptomycin is then exported out of the cell to then be extracted as a useful antibiotic.
References
Streptomycin Biosynthesis References
(n.d.). Retrieved from https://biocyc.org/META/NEW-IMAGE?type=PATHWAY&object=PWY-5940&&ENZORG=TAX-1911&detail-level=0
Distler J, Mansouri K, Mayer G, Stockmann M, Piepersberg W: Streptomycin biosynthesis and its regulation in Streptomycetes. Gene. 1992 Jun 15;115(1-2):105-11. doi: 10.1016/0378-1119(92)90547-3.
Pubmed: 1377151
MAJUMDAR SK, KUTZNER HJ: Studies on the biosynthesis of streptomycin. Appl Microbiol. 1962 Mar;10:157-68.
Pubmed: 14468645
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