KEGG   PATHWAY: rn00521
Entry
rn00521                     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
rn00521  Streptomycin biosynthesis
rn00521

Module
M00793  dTDP-L-Rha biosynthesis, Glc-1P => dTDP-L-Rha [PATH:rn00521]
Drug
D08531  Streptomycin (INN)
Other DBs
GO: 0019872
Reaction
R00299  ATP:D-glucose 6-phosphotransferase
R01183  myo-inositol:NAD+ 2-oxidoreductase
R01187  1D-myo-inositol 3-phosphate phosphohydrolase
R02225  ATP:streptomycin 6-phosphotransferase
R02228  streptomycin-6-phosphate phosphohydrolase
R02328  dTTP:alpha-D-glucose-1-phosphate thymidylyltransferase
R02777  dTDP-beta-L-rhamnose:NADP+ 4-oxidoreductase; dTDP-6-deoxy-L-mannose:NADP+ 4-oxidoreductase
R02781  L-glutamine:2,4,6/3,5-pentahydroxycyclohexanone aminotransferase
R03384  ATP:1-amino-1-deoxy-scyllo-inositol 4-phosphotransferase
R03477  L-arginine:1-amino-1-deoxy-scyllo-inositol-4-phosphate amindinotransferase
R03496  1-guanidino-1-deoxy-scyllo-inositol-4-phosphate 4-phosphohydrolase
R03502  1D-1-guanidino-3-amino-1,3-dideoxy-scyllo-inositol:pyruvate aminotransferase
R04222  dTDP-L-dihydrostreptose:streptidine-6-phosphate dihydrostreptosyltransferase
R05512  
R05515  
R05516  
R05547  
R06365  
R06513  dTDPglucose 4,6-hydro-lyase
R06514  dTDP-4-dehydro-6-deoxy-alpha-D-glucose 3,5-epimerase; dTDP-4-dehydro-6-deoxy-D-glucose 3,5-epimerase
R07324  1D-myo-inositol-3-phosphate lyase (isomerizing)
R08639  alpha-D-glucose 1,6-phosphomutase
R08843  
R08844  ATP:1D-1-guanidino-3-amino-1,3-dideoxy-scyllo-inositol 6-phosphotransferase
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
Related
pathway
rn00523  Polyketide sugar unit biosynthesis
rn00524  Neomycin, kanamycin and gentamicin biosynthesis
KO pathway
ko00521   

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