KEGG   PATHWAY: bfg00524
Entry
bfg00524                    Pathway                                
Name
Neomycin, kanamycin and gentamicin biosynthesis - Bacteroides fragilis 638R
Class
Metabolism; Biosynthesis of other secondary metabolites
Pathway map
bfg00524  Neomycin, kanamycin and gentamicin biosynthesis
bfg00524

Other DBs
GO: 1901158 1901133 1901130
Organism
Bacteroides fragilis 638R [GN:bfg]
Gene
BF638R_2514  putative hexokinase [KO:K00844] [EC:2.7.1.1]
BF638R_0558  glcK; putative ROK family transcriptional repressor [KO:K25026] [EC:2.7.1.2]
BF638R_1750  putative transcriptional repressor [KO:K25026] [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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  Authors
Llewellyn NM, Spencer JB
  Title
Chemoenzymatic acylation of aminoglycoside antibiotics.
  Journal
Chem Commun (Camb) 3786-8 (2008)
DOI:10.1039/b802248h
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)
DOI:10.1007/s10059-009-0080-5
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)
DOI:10.1038/nchembio.671
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)
DOI:10.1039/c2np20092a
Reference
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
Related
pathway
bfg00520  Amino sugar and nucleotide sugar metabolism
bfg00521  Streptomycin biosynthesis
KO pathway
ko00524   

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