Entry
Name
Streptomycin biosynthesis - Shigella flexneri NCTC1 (serotype 2a)
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
BRITE hierarchy
Pathway map
Ortholog table
Module
Other DBs
Organism
Shigella flexneri NCTC1 (serotype 2a) [GN:
sft ]
Gene
NCTC1_00644 pgm; phosphoglucomutase,Phosphoglucomutase, phosphoglucomutase,phosphoglucomutase, alpha-D-glucose phosphate-specific,Phosphoglucomutase/phosphomannomutase, alpha/beta/alpha domain I [KO:K01835 ] [EC:5.4.2.2 ]
NCTC1_02836 suhB; inositol monophosphatase,Inositol-1-monophosphatase,inositol monophosphatase,histidinol-phosphatase,Inositol monophosphatase family [KO:K01092 ] [EC:3.1.3.25 ]
NCTC1_02310 rfbA1; glucose-1-phosphate thymidylyltransferase,Glucose-1-phosphate thymidylyltransferase 1,glucose-1-phosphate thymidylyltransferase RfbA,CTP:phosphocholine cytidylyltransferase involved in choline phosphorylation for cell surface LPS epitopes,glucose-1-phosphate thymidylyltransferase,Nucleotidyl transferase [KO:K00973 ] [EC:2.7.7.24 ]
NCTC1_04175 rfbA; glucose-1-phosphate thymidylyltransferase,Glucose-1-phosphate thymidylyltransferase 2,glucose-1-phosphate thymidylyltransferase RfbA,GTP:adenosylcobinamide-phosphate guanylyltransferase,glucose-1-phosphate thymidylyltransferase,Nucleotidyl transferase [KO:K00973 ] [EC:2.7.7.24 ]
NCTC1_02312 rfbB2; dTDP-glucose-4,6-dehydratase,dTDP-glucose 4,6-dehydratase,dTDP-glucose 4,6 dehydratase,dTDP-glucose 4,6-dehydratase,NAD dependent epimerase/dehydratase family [KO:K01710 ] [EC:4.2.1.46 ]
NCTC1_04174 rffG; dTDP-glucose 4,6-dehydratase,dTDP-glucose 4,6-dehydratase 2,dTDP-glucose 4,6-dehydratase,dTDP-glucose 4,6-dehydratase,NAD dependent epimerase/dehydratase family [KO:K01710 ] [EC:4.2.1.46 ]
NCTC1_02309 rfbC; dTDP-4-dehydrorhamnose 3,5-epimerase,dTDP-4-dehydrorhamnose 3,5-epimerase,dTDP-4-dehydrorhamnose 3,5-epimerase [KO:K01790 ] [EC:5.1.3.13 ]
NCTC1_02311 rfbD; dTDP-4-dehydrorhamnose reductase,dTDP-4-dehydrorhamnose reductase,dTDP-4-dehydrorhamnose reductase,RmlD substrate binding domain [KO:K00067 ] [EC:1.1.1.133 ]
Compound
C00688 dTDP-4-dehydro-beta-L-rhamnose
C00691 2,4,6/3,5-Pentahydroxycyclohexanone
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
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
Authors
Wehmeier UF, Piepersberg W
Title
Enzymology of aminoglycoside biosynthesis-deduction from gene clusters.
Journal
Reference
Authors
Flatt PM, Mahmud T
Title
Biosynthesis of aminocyclitol-aminoglycoside antibiotics and related compounds.
Journal
Reference
Authors
Walker JB
Title
Possible evolutionary relationships between streptomycin and bluensomycin biosynthetic pathways: detection of novel inositol kinase and O-carbamoyltransferase activities.
Journal
Reference
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
Reference
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
Reference
Authors
Distler J, Mansouri K, Mayer G, Stockmann M, Piepersberg W
Title
Streptomycin biosynthesis and its regulation in Streptomycetes.
Journal
Reference
Authors
Mansouri K, Piepersberg W.
Title
Genetics of streptomycin production in Streptomyces griseus: nucleotide sequence of five genes, strFGHIK, including a phosphatase gene.
Journal
Reference
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
Related pathway
sft00523 Polyketide sugar unit biosynthesis
KO pathway
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