KEGG   PATHWAY: ko00524Help
Entry
ko00524                     Pathway                                

Name
Neomycin, kanamycin and gentamicin biosynthesis
Class
Metabolism; Biosynthesis of other secondary metabolites
BRITE hierarchy
Pathway map
Neomycin, kanamycin and gentamicin biosynthesis
ko00524

All organismsOrtholog table
Orthology
K00844  
hexokinase [EC:2.7.1.1]
K12407  
glucokinase [EC:2.7.1.2]
K00845  
glucokinase [EC:2.7.1.2]
K13546  
2-deoxy-scyllo-inosose synthase [EC:4.2.3.124]
K13547  
L-glutamine:2-deoxy-scyllo-inosose/3-amino-2,3-dideoxy-scyllo-inosose aminotransferase [EC:2.6.1.101 2.6.1.100]
K13548  
2-deoxy-scyllo-inosamine dehydrogenase [EC:1.1.1.329]
K13549  
2-deoxy-scyllo-inosamine dehydrogenase (SAM-dependent) [EC:1.1.99.38]
K13550  
2-deoxystreptamine N-acetyl-D-glucosaminyltransferase / 2-deoxystreptamine glucosyltransferase [EC:2.4.1.284 2.4.1.283]
K13551  
2'-N-acetylparomamine deacetylase [EC:3.5.1.112]
K17078  
2'-N-acetylparomamine deacetylase / 2'''-acetyl-6'''-hydroxyneomycin deacetylase [EC:3.5.1.113 3.5.1.112]
K13552  
paromamine 6'-oxidase [EC:1.1.3.43]
K20565  
paromamine 6'-oxidase / 6'''-hydroxyneomycin C oxidase [EC:1.1.3.44 1.1.3.43]
K20566  
paromamine 6'-oxidase / 2'-deamino-2'-hydroxyparomamine 6'-oxidase [EC:1.1.3.- 1.1.3.43]
K13553  
neamine transaminase [EC:2.6.1.93]
K20567  
neamine transaminase / neomycin C transaminase [EC:2.6.1.95 2.6.1.93]
K20568  
neamine transaminase / 2'-deamino-2'-hydroxyneamine transaminase [EC:2.6.1.94 2.6.1.93]
K13554  
neamine phosphoribosyltransferase [EC:2.4.2.49]
K13555  
5''-phosphoribostamycin phosphatase [EC:3.1.3.88]
K13556  
UDP-N-acetyl-D-glucosamine:ribostamycin N-acetyl-D-glucosaminyltransferase [EC:2.4.1.285]
K13557  
neomycin C epimerase [EC:5.1.3.-]
K13559  
[BtrI acyl-carrier protein]--L-glutamate ligase [EC:6.2.1.39]
K13560  
L-glutamyl-[BtrI acyl-carrier protein] decarboxylase [EC:4.1.1.95]
K13561  
4-(gamma-L-glutamylamino)butanoyl-[BtrI acyl-carrier protein] monooxygenase [EC:1.14.14.13]
K13562  
NAD(P)H:FMN oxidoreductase [EC:1.5.1.-]
K13563  
ribostamycin:4-(gamma-L-glutamylamino)-(S)-2-hydroxybutanoyl-[BtrI acyl-carrier protein] 4-(gamma-L-glutamylamino)-(S)-2-hydroxybutanoate transferase [EC:2.3.2.19]
K13564  
gamma-L-glutamyl-butirosin B gamma-L-glutamyl cyclotransferase [EC:4.3.2.6]
K20569  
NAD+-dependent dehydrogenase [EC:1.1.1.-]
K20570  
NADPH-dependent reductase [EC:1.1.1.-]
K20571  
dehydrogenase [EC:1.1.1.-]
K20572  
aminotransferase [EC:2.6.1.-]
K20573  
2'-deamino-2'-hydroxyneamine 1-alpha-D-kanosaminyltransferase [EC:2.4.1.301]
K20574  
kanamycin B dioxygenase [EC:1.14.11.37]
K20152  
2'-dehydrokanamycin reductase [EC:1.1.1.355]
K20575  
radical SAM diol-dehydratase
K20576  
NADP-dependent dehydrogenase [EC:1.1.1.-]
K20577  
paromamine/lividamine 6'-oxidase [EC:1.1.3.- 1.1.3.43]
K20578  
glycosyltransferase [EC:2.4.1.-]
K20579  
nebramycin 5' synthase [EC:6.1.2.2]
K20580  
phosphoribosyltransferase [EC:2.4.2.-]
K20581  
phosphatase [EC:3.1.3.-]
K20582  
N-acetylglucosaminyltransferase [EC:2.4.1.-]
K20583  
deacetylase [EC:3.5.1.-]
K20584  
6'''-hydroxyparomomycin oxidase [EC:1.1.3.-]
K20585  
paromomycin transaminase [EC:2.6.1.-]
K20586  
oxidoreductase
K20587  
dehydrogenase
K20588  
5'''-epimerase [EC:5.1.3.-]
K20589  
paromamine D-xylosyltransferase [EC:2.4.2.-]
K20590  
gentamicin A2 dehydrogenase [EC:1.1.1.-]
K20591  
pyridoxal phosphate-dependent aminotransferase [EC:2.6.1.-]
K20592  
SAM-dependent 3''-N-methyltransferase [EC:2.1.1.-]
K20593  
cobalamin-dependent radical SAM methyltransferase [EC:2.1.1.-]
K20594  
cobalamin-dependent radical SAM methyltransferase [EC:2.1.1.-]
K20595  
gentamicin-X2/G418 6'-oxidase
K20596  
JI-20A/JI-20Ba transaminase [EC:2.6.1.-]
K20597  
JI-20B transaminase / epimerase [EC:2.6.1.-]
K20598  
aminoglycoside phosphotransferase
Compound
C00025  
L-Glutamate
C00029  
UDP-glucose
C00031  
D-Glucose
C00043  
UDP-N-acetyl-alpha-D-glucosamine
C00092  
D-Glucose 6-phosphate
C00229  
Acyl-carrier protein
C00397  
Tobramycin
C00825  
Kanamycin B
C00832  
Paromomycin
C00908  
Gentamicin C1a
C01441  
Neamine
C01555  
Apramycin
C01737  
Neomycin B
C01743  
Paromamine
C01759  
Ribostamycin
C01822  
Kanamycin A
C01823  
Kanamycin C
C01917  
Gentamicin A
C02033  
Gentamicin C2
C02627  
2-Deoxystreptamine
C07656  
Gentamicin C1
C12210  
UDP-3-ketoglucose
C12211  
UDP-kanosamine
C15652  
Neomycin C
C17209  
2-Deoxy-scyllo-inosose
C17580  
2-Deoxy-scyllo-inosamine
C17581  
3-Amino-2,3-dideoxy-scyllo-inosose
C17582  
2'-N-Acetylparomamine
C17583  
6'-Dehydro-6'-oxoparomamine
C17584  
Xylostasin
C17585  
Butirosin A
C17586  
Butirosin B
C17587  
2'''-N-Acetyl-6'''-deamino-6'''-hydroxyneomycin C
C17588  
6'''-Deamino-6'''-hydroxyneomycin C
C17589  
6'''-Deamino-6'''-oxoneomycin C
C17701  
Gentamicin A2
C17702  
Gentamicin X2
C17703  
Antibiotic G-418
C17704  
Antibiotic JI-20A
C17705  
Antibiotic JI-20B
C17706  
Gentamicin C2b
C17707  
Lividomycin A
C17712  
Paromomycin II
C17997  
Oxyapramycin
C18000  
Nebramycin factor 4
C18001  
Nebramycin 5'
C18002  
5-Ribosylparomamine
C18003  
Lividomycin B
C18004  
5''-Phosphoribostamycin
C18005  
gamma-L-Glutamyl-butirosin B
C18006  
gamma-L-Glutamyl-[acp]
C18007  
4-Aminobutyryl-[acp]
C18008  
4-(gamma-L-Glutamylamino)butanoyl-[acp]
C18009  
4-(gamma-L-Glutamylamino)-(2S)-2-hydroxybutanoyl-[acp]
C20350  
2'-Deamino-2'-hydroxyneamine
C20351  
2'-Deamino-2'-hydroxy-6'-dehydroparomamine
C20353  
2'-Deamino-2'-hydroxyparomamine
C20509  
2'-Dehydrokanamycin A
C20614  
Kanamycin X
C20699  
6''-O-Carbamoylkanamycin A
C21176  
3''-Oxoribostamycin
C21251  
6'-Oxokanamycin X
C21252  
6'-Oxokanamycin C
C21253  
Kanamycin D
C21254  
3''-Deamino-3''-hydroxykanamycin B
C21255  
Lividamine
C21256  
6'-Oxolividamine
C21257  
4'-Oxolividamine
C21258  
4'-Oxonebramine
C21259  
Nebramine
C21260  
5''-Phosphoribosylparomamine
C21261  
2'''-N-Acetyl-6'''-deamino-6'''-hydroxyparomomycin II
C21262  
6'''-Deamino-6'''-hydroxyparomomycin II
C21263  
6'''-Deamino-6'''-oxoparomomycin II
C21264  
5'''-epi-Lividomycin B
C21265  
3''-Oxogentamicin A2
C21266  
3''-Amino-3''-deoxygentamicin A2
C21267  
6'-Oxogentamicin X2
C21268  
6'-Oxo-G418
C21269  
Antibiotic JI-20Ba
C21270  
Gentamicin C2a
Reference
  Authors
Kudo F, Eguchi T
  Title
Biosynthetic enzymes for the aminoglycosides butirosin and neomycin.
  Journal
Methods Enzymol 459:493-519 (2009)
Reference
  Authors
Kudo F, Eguchi T
  Title
Biosynthetic genes for aminoglycoside antibiotics.
  Journal
J Antibiot (Tokyo) 62:471-81 (2009)
Reference
  Authors
Nango E, Kumasaka T, Hirayama T, Tanaka N, Eguchi T
  Title
Structure of 2-deoxy-scyllo-inosose synthase, a key enzyme in the biosynthesis of 2-deoxystreptamine-containing aminoglycoside antibiotics, in complex with a mechanism-based inhibitor and NAD+.
  Journal
Proteins 70:517-27 (2008)
Reference
  Authors
Yokoyama K, Kudo F, Kuwahara M, Inomata K, Tamegai H, Eguchi T, Kakinuma K
  Title
Stereochemical recognition of doubly functional aminotransferase in 2-deoxystreptamine biosynthesis.
  Journal
J Am Chem Soc 127:5869-74 (2005)
Reference
  Authors
Tamegai H, Nango E, Kuwahara M, Yamamoto H, Ota Y, Kuriki H, Eguchi T, Kakinuma K
  Title
Identification of L-glutamine: 2-deoxy-scyllo-inosose aminotransferase required for the biosynthesis of butirosin in Bacillus circulans.
  Journal
J Antibiot (Tokyo) 55:707-14 (2002)
Reference
  Authors
Kudo F, Yamamoto Y, Yokoyama K, Eguchi T, Kakinuma K
  Title
Biosynthesis of 2-deoxystreptamine by three crucial enzymes in Streptomyces fradiae NBRC 12773.
  Journal
J Antibiot (Tokyo) 58:766-74 (2005)
Reference
  Authors
Yokoyama K, Ohmori D, Kudo F, Eguchi T
  Title
Mechanistic study on the reaction of a radical SAM dehydrogenase BtrN by electron paramagnetic resonance spectroscopy.
  Journal
Biochemistry 47:8950-60 (2008)
Reference
  Authors
Yokoyama K, Numakura M, Kudo F, Ohmori D, Eguchi T
  Title
Characterization and mechanistic study of a radical SAM dehydrogenase in the biosynthesis of butirosin.
  Journal
J Am Chem Soc 129:15147-55 (2007)
Reference
  Authors
Yokoyama K, Yamamoto Y, Kudo F, Eguchi T
  Title
Involvement of two distinct N-acetylglucosaminyltransferases and a dual-function  deacetylase in neomycin biosynthesis.
  Journal
Chembiochem 9:865-9 (2008)
Reference
  Authors
Fan Q, Huang F, Leadlay PF, Spencer JB
  Title
The neomycin biosynthetic gene cluster of Streptomyces fradiae NCIMB 8233: genetic and biochemical evidence for the roles of two glycosyltransferases and a deacetylase.
  Journal
Org Biomol Chem 6:3306-14 (2008)
Reference
  Authors
Truman AW, Huang F, Llewellyn NM, Spencer JB
  Title
Characterization of the enzyme BtrD from Bacillus circulans and revision of its functional assignment in the biosynthesis of butirosin.
  Journal
Angew Chem Int Ed Engl 46:1462-4 (2007)
Reference
  Authors
Kudo F, Fujii T, Kinoshita S, Eguchi T
  Title
Unique O-ribosylation in the biosynthesis of butirosin.
  Journal
Bioorg Med Chem 15:4360-8 (2007)
Reference
  Authors
Yukita T, Nishida H, Eguchi T, Kakinuma K
  Title
Biosynthesis of (2R)-4-amino-2-hydroxybutyric acid, unique and biologically significant substituent in butirosins.
  Journal
J Antibiot (Tokyo) 56:497-500 (2003)
Reference
  Authors
Li Y, Llewellyn NM, Giri R, Huang F, Spencer JB
  Title
Biosynthesis of the unique amino acid side chain of butirosin: possible protective-group chemistry in an acyl carrier protein-mediated pathway.
  Journal
Chem Biol 12:665-75 (2005)
Reference
  Authors
Llewellyn NM, Li Y, Spencer JB
  Title
Biosynthesis of butirosin: transfer and deprotection of the unique amino acid side chain.
  Journal
Chem Biol 14:379-86 (2007)
Reference
  Authors
Llewellyn NM, Spencer JB
  Title
Chemoenzymatic acylation of aminoglycoside antibiotics.
  Journal
Chem Commun (Camb) 3786-8 (2008)
Reference
  Authors
Nepal KK, Oh TJ, Sohng JK
  Title
Heterologous production of paromamine in Streptomyces lividans TK24 using kanamycin biosynthetic genes from Streptomyces kanamyceticus ATCC12853.
  Journal
Mol Cells 27:601-8 (2009)
Reference
  Authors
Park JW, Park SR, Nepal KK, Han AR, Ban YH, Yoo YJ, Kim EJ, Kim EM, Kim D, Sohng JK, Yoon YJ
  Title
Discovery of parallel pathways of kanamycin biosynthesis allows antibiotic manipulation.
  Journal
Nat Chem Biol 7:843-52 (2011)
Reference
  Authors
Arya DP (ed).
  Title
Aminoglycoside antibiotics: From chemical biology to drug discovery
  Journal
Wiley-Interscience (2007)
Reference
  Authors
Park SR, Park JW, Ban YH, Sohng JK, Yoon YJ
  Title
2-Deoxystreptamine-containing aminoglycoside antibiotics: recent advances in the  characterization and manipulation of their biosynthetic pathways.
  Journal
Nat Prod Rep 30:11-20 (2013)
Reference
  Authors
Llewellyn NM, Spencer JB
  Title
Biosynthesis of 2-deoxystreptamine-containing aminoglycoside antibiotics.
  Journal
Nat Prod Rep 23:864-74 (2006)
Reference
  Authors
Kudo F, Eguchi T
  Title
Aminoglycoside Antibiotics: New Insights into the Biosynthetic Machinery of Old Drugs.
  Journal
Chem Rec 16:4-18 (2016)
Reference
  Authors
Takeishi R, Kudo F, Numakura M, Eguchi T
  Title
Epimerization at C-3'' in butirosin biosynthesis by an NAD(+) -dependent dehydrogenase BtrE and an NADPH-dependent reductase BtrF.
  Journal
Chembiochem 16:487-95 (2015)
Reference
  Authors
Lv M, Ji X, Zhao J, Li Y, Zhang C, Su L, Ding W, Deng Z, Yu Y, Zhang Q
  Title
Characterization of a C3 Deoxygenation Pathway Reveals a Key Branch Point in Aminoglycoside Biosynthesis.
  Journal
J Am Chem Soc 138:6427-35 (2016)
Reference
  Authors
Clausnitzer D, Piepersberg W, Wehmeier UF
  Title
The oxidoreductases LivQ and NeoQ are responsible for the different 6'-modifications in the aminoglycosides lividomycin and neomycin.
  Journal
J Appl Microbiol 111:642-51 (2011)
Reference
  Authors
Park JW, Hong JS, Parajuli N, Jung WS, Park SR, Lim SK, Sohng JK, Yoon YJ
  Title
Genetic dissection of the biosynthetic route to gentamicin A2 by heterologous expression of its minimal gene set.
  Journal
Proc Natl Acad Sci U S A 105:8399-404 (2008)
Reference
  Authors
Huang C, Huang F, Moison E, Guo J, Jian X, Duan X, Deng Z, Leadlay PF, Sun Y
  Title
Delineating the biosynthesis of gentamicin x2, the common precursor of the gentamicin C antibiotic complex.
  Journal
Chem Biol 22:251-61 (2015)
Reference
  Authors
Guo J, Huang F, Huang C, Duan X, Jian X, Leeper F, Deng Z, Leadlay PF, Sun Y
  Title
Specificity and promiscuity at the branch point in gentamicin biosynthesis.
  Journal
Chem Biol 21:608-18 (2014)
Reference
  Authors
Gu Y, Ni X, Ren J, Gao H, Wang D, Xia H
  Title
Biosynthesis of Epimers C2 and C2a in the Gentamicin C Complex.
  Journal
Chembiochem (2015)
Reference
  Authors
Kim HJ, McCarty RM, Ogasawara Y, Liu YN, Mansoorabadi SO, LeVieux J, Liu HW
  Title
GenK-catalyzed C-6' methylation in the biosynthesis of gentamicin: isolation and  characterization of a cobalamin-dependent radical SAM enzyme.
  Journal
J Am Chem Soc 135:8093-6 (2013)

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