ENTRY       hsa00524                    Pathway
NAME        Neomycin, kanamycin and gentamicin biosynthesis - Homo sapiens (human)
CLASS       Metabolism; Biosynthesis of other secondary metabolites
PATHWAY_MAP hsa00524  Neomycin, kanamycin and gentamicin biosynthesis
DBLINKS     GO: 1901158 1901133 1901130
ORGANISM    Homo sapiens (human) [GN:hsa]
GENE        3101  HK3; hexokinase 3 [KO:K00844] [EC:2.7.1.1]
            3098  HK1; hexokinase 1 [KO:K00844] [EC:2.7.1.1]
            3099  HK2; hexokinase 2 [KO:K00844] [EC:2.7.1.1]
            80201  HKDC1; hexokinase domain containing 1 [KO:K00844] [EC:2.7.1.1]
            2645  GCK; glucokinase [KO:K12407] [EC:2.7.1.2]
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   PMID:19362652
  AUTHORS   Kudo F, Eguchi T
  TITLE     Biosynthetic enzymes for the aminoglycosides butirosin and neomycin.
  JOURNAL   Methods Enzymol 459:493-519 (2009)
            DOI:10.1016/S0076-6879(09)04620-5
REFERENCE   PMID:19644520
  AUTHORS   Kudo F, Eguchi T
  TITLE     Biosynthetic genes for aminoglycoside antibiotics.
  JOURNAL   J Antibiot (Tokyo) 62:471-81 (2009)
            DOI:10.1038/ja.2009.76
REFERENCE   PMID:17879343
  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)
            DOI:10.1002/prot.21526
REFERENCE   PMID:15839685
  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)
            DOI:10.1021/ja0445948
REFERENCE   PMID:12374384
  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)
            DOI:10.7164/antibiotics.55.707
REFERENCE   PMID:16506694
  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)
            DOI:10.1038/ja.2005.104
REFERENCE   PMID:18672902
  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)
            DOI:10.1021/bi800509x
REFERENCE   PMID:18001019
  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)
            DOI:10.1021/ja072481t
REFERENCE   PMID:18311744
  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)
            DOI:10.1002/cbic.200700717
REFERENCE   PMID:18802637
  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)
            DOI:10.1039/b808734b
REFERENCE   PMID:17226887
  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)
            DOI:10.1002/anie.200604194
REFERENCE   PMID:17482823
  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)
            DOI:10.1016/j.bmc.2007.04.040
REFERENCE   PMID:12870817
  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)
            DOI:10.7164/antibiotics.56.497
REFERENCE   PMID:15975512
  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)
            DOI:10.1016/j.chembiol.2005.04.010
REFERENCE   PMID:17462573
  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)
            DOI:10.1016/j.chembiol.2007.02.005
REFERENCE   PMID:18685777
  AUTHORS   Llewellyn NM, Spencer JB
  TITLE     Chemoenzymatic acylation of aminoglycoside antibiotics.
  JOURNAL   Chem Commun (Camb) 3786-8 (2008)
            DOI:10.1039/b802248h
REFERENCE   PMID:19466609
  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)
            DOI:10.1007/s10059-009-0080-5
REFERENCE   PMID:21983602
  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)
            DOI:10.1038/nchembio.671
REFERENCE   
  AUTHORS   Arya DP (ed).
  TITLE     Aminoglycoside antibiotics: From chemical biology to drug discovery
  JOURNAL   Wiley-Interscience (2007)
REFERENCE   PMID:23179168
  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)
            DOI:10.1039/c2np20092a
REFERENCE   PMID:17119636
  AUTHORS   Llewellyn NM, Spencer JB
  TITLE     Biosynthesis of 2-deoxystreptamine-containing aminoglycoside antibiotics.
  JOURNAL   Nat Prod Rep 23:864-74 (2006)
            DOI:10.1039/b604709m
REFERENCE   PMID:26455715
  AUTHORS   Kudo F, Eguchi T
  TITLE     Aminoglycoside Antibiotics: New Insights into the Biosynthetic Machinery of Old Drugs.
  JOURNAL   Chem Rec 16:4-18 (2016)
            DOI:10.1002/tcr.201500210
REFERENCE   PMID:25600434
  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)
            DOI:10.1002/cbic.201402612
REFERENCE   PMID:27120352
  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)
            DOI:10.1021/jacs.6b02221
REFERENCE   PMID:21689223
  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)
            DOI:10.1111/j.1365-2672.2011.05082.x
REFERENCE   PMID:18550838
  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)
            DOI:10.1073/pnas.0803164105
REFERENCE   PMID:25641167
  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)
            DOI:10.1016/j.chembiol.2014.12.012
REFERENCE   PMID:24746560
  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)
            DOI:10.1016/j.chembiol.2014.03.005
REFERENCE   PMID:26083124
  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 16:1933-42 (2015)
            DOI:10.1002/cbic.201500258
REFERENCE   PMID:23679096
  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)
            DOI:10.1021/ja312641f
REL_PATHWAY hsa00520  Amino sugar and nucleotide sugar metabolism
KO_PATHWAY  ko00524
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