ENTRY ko00521 Pathway NAME Streptomycin biosynthesis DESCRIPTION Streptomycin is an aminocyclitol-aminoglycoside antibiotic produced by Streptomyces griseus. Streptomycin consists of aminocyclitol (streptidine), 6-deoxyhexose (streptose), and N-methyl-L-glucosamine moieties, which are formed by independent biosynthetic pathways. All of the moieties are derived from D-glucose. The streptidine moiety is synthesized via myo-inositol, which is then oxidized at C-1 and transaminated to give scyllo-inosamine. After phosphorylation, the compound is transamidinated by arginine. The same procedure is repeated at the C-3 position. The streptose moiety is made from D-glucose via a dTDP-glucose pathway. The exact biosynthetic route for the N-methyl-L-glucosamine moiety is unknown, though the biosynthetic gene cluster have been proposed. CLASS Metabolism; Biosynthesis of other secondary metabolites PATHWAY_MAP ko00521 Streptomycin biosynthesis MODULE M00793 dTDP-L-rhamnose biosynthesis [PATH:ko00521] DBLINKS GO: 0019872 ORTHOLOGY K00844 hexokinase [EC:2.7.1.1] K12407 glucokinase [EC:2.7.1.2] K00845 glucokinase [EC:2.7.1.2] K25026 glucokinase [EC:2.7.1.2] K01835 phosphoglucomutase [EC:5.4.2.2] K15778 phosphomannomutase / phosphoglucomutase [EC:5.4.2.8 5.4.2.2] K01858 myo-inositol-1-phosphate synthase [EC:5.5.1.4] K01092 myo-inositol-1(or 4)-monophosphatase [EC:3.1.3.25] K00010 myo-inositol 2-dehydrogenase / D-chiro-inositol 1-dehydrogenase [EC:1.1.1.18 1.1.1.369] K05957 L-glutamine:scyllo-inosose aminotransferase [EC:2.6.1.50] K04339 scyllo-inosamine 4-kinase [EC:2.7.1.65] K04340 scyllo-inosamine-4-phosphate amidinotransferase 1 [EC:2.1.4.2] K00973 glucose-1-phosphate thymidylyltransferase [EC:2.7.7.24] K23144 UDP-N-acetylglucosamine diphosphorylase / glucose-1-phosphate thymidylyltransferase / UDP-N-acetylgalactosamine diphosphorylase / glucosamine-1-phosphate N-acetyltransferase / galactosamine-1-phosphate N-acetyltransferase [EC:2.7.7.23 2.7.7.24 2.7.7.83 2.3.1.157 2.3.1.276] K01710 dTDP-glucose 4,6-dehydratase [EC:4.2.1.46] K01790 dTDP-4-dehydrorhamnose 3,5-epimerase [EC:5.1.3.13] K00067 dTDP-4-dehydrorhamnose reductase [EC:1.1.1.133] K23987 dTDP-4-dehydrorhamnose 3,5-epimerase/reductase [EC:5.1.3.13 1.1.1.133] K04341 dTDP-dihydrostreptose-streptidine-6-phosphate dihydrostreptosyltransferase [EC:2.4.2.27] K04342 streptomycin-6-phosphatase [EC:3.1.3.39] K12570 streptomycin 6-kinase [EC:2.7.1.72] COMPOUND C00031 D-Glucose C00092 D-Glucose 6-phosphate C00103 D-Glucose 1-phosphate C00137 myo-Inositol C00413 Streptomycin C00688 dTDP-4-dehydro-beta-L-rhamnose C00691 2,4,6/3,5-Pentahydroxycyclohexanone C00842 dTDP-glucose C01121 Streptidine 6-phosphate C01138 Streptomycin 6-phosphate C01214 1-Amino-1-deoxy-scyllo-inositol C01221 Dihydrostreptomycin 6-phosphate C01283 1-Amino-1-deoxy-scyllo-inositol 4-phosphate C01294 1-Guanidino-1-deoxy-scyllo-inositol 4-phosphate C01298 1D-1-Guanidino-3-amino-1,3-dideoxy-scyllo-inositol C03319 dTDP-L-rhamnose C03442 dTDP-L-dihydrostreptose C04006 1D-myo-Inositol 3-phosphate C04280 1-Guanidino-1-deoxy-scyllo-inositol C04673 1D-1-Guanidino-1-deoxy-3-dehydro-scyllo-inositol C04767 O-(1->4)-alpha-L-Dihydrostreptosyl-streptidine 6-phosphate C06592 NDP-N-methyl-L-glucosamine C11351 N1-Amidinostreptamine 6-phosphate C11907 dTDP-4-oxo-6-deoxy-D-glucose REFERENCE PMID:19362651 AUTHORS Wehmeier UF, Piepersberg W TITLE Enzymology of aminoglycoside biosynthesis-deduction from gene clusters. JOURNAL Methods Enzymol 459:459-91 (2009) DOI:10.1016/S0076-6879(09)04619-9 REFERENCE PMID:17390001 AUTHORS Flatt PM, Mahmud T TITLE Biosynthesis of aminocyclitol-aminoglycoside antibiotics and related compounds. JOURNAL Nat Prod Rep 24:358-92 (2007) DOI:10.1039/b603816f REFERENCE PMID:1698764 AUTHORS Walker JB TITLE Possible evolutionary relationships between streptomycin and bluensomycin biosynthetic pathways: detection of novel inositol kinase and O-carbamoyltransferase activities. JOURNAL J Bacteriol 172:5844-51 (1990) DOI:10.1128/JB.172.10.5844-5851.1990 REFERENCE PMID:2995326 AUTHORS Ohnuki T, Imanaka T, Aiba S TITLE Self-cloning in Streptomyces griseus of an str gene cluster for streptomycin biosynthesis and streptomycin resistance. JOURNAL J Bacteriol 164:85-94 (1985) DOI:10.1128/JB.164.1.85-94.1985 REFERENCE PMID:9238101 AUTHORS Ahlert J, Distler J, Mansouri K, Piepersberg W TITLE Identification of stsC, the gene encoding the L-glutamine:scyllo-inosose aminotransferase from streptomycin-producing Streptomycetes. JOURNAL Arch Microbiol 168:102-13 (1997) DOI:10.1007/s002030050475 REFERENCE PMID:1377151 AUTHORS Distler J, Mansouri K, Mayer G, Stockmann M, Piepersberg W TITLE Streptomycin biosynthesis and its regulation in Streptomycetes. JOURNAL Gene 115:105-11 (1992) DOI:10.1016/0378-1119(92)90547-3 REFERENCE PMID:1654502 AUTHORS Mansouri K, Piepersberg W. TITLE Genetics of streptomycin production in Streptomyces griseus: nucleotide sequence of five genes, strFGHIK, including a phosphatase gene. JOURNAL Mol Gen Genet 228:459-69 (1991) DOI:10.1007/BF00260640 REFERENCE PMID:9922132 AUTHORS Fritsche E, Bergner A, Humm A, Piepersberg W, Huber R TITLE Crystal structure of L-arginine:inosamine-phosphate amidinotransferase StrB1 from Streptomyces griseus: an enzyme involved in streptomycin biosynthesis. JOURNAL Biochemistry 37:17664-72 (1998) DOI:10.1021/bi981949p REL_PATHWAY ko00523 Polyketide sugar unit biosynthesis ko00524 Neomycin, kanamycin and gentamicin biosynthesis ///