KEGG   ORTHOLOGY: K14257Help
Entry
K14257                      KO                                     

Name
ctcP, cts4, prnC
Definition
tetracycline 7-halogenase / FADH2 O2-dependent halogenase [EC:1.14.19.49 1.14.19.-]
Pathway
ko00253  Tetracycline biosynthesis
ko00404  Staurosporine biosynthesis
ko01057  Biosynthesis of type II polyketide products
ko01100  Metabolic pathways
ko01130  Biosynthesis of antibiotics
Module
M00790  Pyrrolnitrin biosynthesis, tryptophan => pyrrolnitrin
M00823  Chlortetracycline biosynthesis, pretetramide => chlortetracycline
Brite
KEGG Orthology (KO) [BR:ko00001]
 09100 Metabolism
  09109 Metabolism of terpenoids and polyketides
   01057 Biosynthesis of type II polyketide products
    K14257  ctcP, cts4, prnC; tetracycline 7-halogenase / FADH2 O2-dependent halogenase
   00253 Tetracycline biosynthesis
    K14257  ctcP, cts4, prnC; tetracycline 7-halogenase / FADH2 O2-dependent halogenase
  09110 Biosynthesis of other secondary metabolites
   00404 Staurosporine biosynthesis
    K14257  ctcP, cts4, prnC; tetracycline 7-halogenase / FADH2 O2-dependent halogenase
Enzymes [BR:ko01000]
 1. Oxidoreductases
  1.14  Acting on paired donors, with incorporation or reduction of molecular oxygen
   1.14.19  With oxidation of a pair of donors resulting in the reduction of O2 to two molecules of water
    1.14.19.49  tetracycline 7-halogenase
     K14257  ctcP, cts4, prnC; tetracycline 7-halogenase / FADH2 O2-dependent halogenase
    1.14.19.-  
     K14257  ctcP, cts4, prnC; tetracycline 7-halogenase / FADH2 O2-dependent halogenase
BRITE hierarchy
Other DBs
RN: R05456 R11106 R11478
COG: COG0644
Genes
ENO: ECENHK_14345
ECLN: ECNIH4_08285
SRR: SerAS9_4266
SRL: SOD_c39980(prnC)
SRY: M621_21735
SPLY: Q5A_021590(soxA)
SRS: SerAS12_4267
SRA: SerAS13_4267
SMAF: D781_2599
SRZ: AXX16_2518
PAF: PAM18_2383(pltM)
PAEL: T223_13175
PFL: PFL_2784(pltM) PFL_3606(prnC)
PPRC: PFLCHA0_c28420(pltM) PFLCHA0_c36470(prnC)
PPRO: PPC_2829(pltM) PPC_3745(prnC)
PSEM: TO66_16625
CJA: CJA_2999(halA)
HCH: HCH_02500
BMA: BMAA1201(prnC)
BMV: BMASAVP1_0165(prnC)
BML: BMA10229_0442(prnC)
BMN: BMA10247_A1135(prnC)
BMAL: DM55_4314
BMAE: DM78_3855
BMAQ: DM76_3266
BMAI: DM57_4424
BMAF: DM51_4862
BMAZ: BM44_4276
BMAB: BM45_3400
BPS: BPSS1010
BTZ: BTL_5468
BTHA: DR62_5268
BOC: BG90_2527
BAM: Bamb_4728
BCON: NL30_32790
BUB: BW23_5780
BSEM: WJ12_18240
BMEC: WJ16_17190
MAB: MAB_2284
MABB: MASS_2208
MSTE: MSTE_02497
NNO: NONO_c51090(prnC)
SCO: SCO1275(2SCG18.22)
SCT: SCAT_5600
SVE: SVEN_0488
SFI: SFUL_3996
SAMB: SAM23877_1355(prnC)
FAL: FRAAL0926
SEN: SACE_4927
ASE: ACPL_6150
ACTS: ACWT_6018
CAI: Caci_3552
AMR: AM1_6083
CTHE: Chro_3657
RBA: RB1653(prnC)
RUL: UC8_31640
ABAS: ACPOL_5987
GBA: J421_4025
RMR: Rmar_2072
CPRV: CYPRO_2187
AG: AAB97506(prnC) AEI98659(ctcP) BAA07389(cts4)
 » show all
TaxonomyKoalaUniProt
Reference
PMID:7612997 (cts4)
  Authors
Dairi T, Nakano T, Aisaka K, Katsumata R, Hasegawa M.
  Title
Cloning and nucleotide sequence of the gene responsible for chlorination of tetracycline.
  Journal
Biosci Biotechnol Biochem 59:1099-106 (1995)
DOI:10.1271/bbb.59.1099
  Sequence
Reference
PMID:9172332 (prnC)
  Authors
Hammer PE, Hill DS, Lam ST, Van Pee KH, Ligon JM
  Title
Four genes from Pseudomonas fluorescens that encode the biosynthesis of pyrrolnitrin.
  Journal
Appl Environ Microbiol 63:2147-54 (1997)
  Sequence
Reference
PMID:23800859 (ctcP)
  Authors
Zhu T, Cheng X, Liu Y, Deng Z, You D
  Title
Deciphering and engineering of the final step halogenase for improved chlortetracycline biosynthesis in industrial Streptomyces aureofaciens.
  Journal
Metab Eng 19:69-78 (2013)
DOI:10.1016/j.ymben.2013.06.003
  Sequence
Reference
  Authors
Vaillancourt FH, Yeh E, Vosburg DA, Garneau-Tsodikova S, Walsh CT
  Title
Nature's inventory of halogenation catalysts: oxidative strategies predominate.
  Journal
Chem Rev 106:3364-78 (2006)
DOI:10.1021/cr050313i

KEGG   ORTHOLOGY: K21297Help
Entry
K21297                      KO                                     

Name
ctcQ
Definition
flavin reductase (NADH) [EC:1.5.1.36]
Pathway
ko00253  Tetracycline biosynthesis
ko01057  Biosynthesis of type II polyketide products
ko01100  Metabolic pathways
ko01130  Biosynthesis of antibiotics
Module
M00823  Chlortetracycline biosynthesis, pretetramide => chlortetracycline
Brite
KEGG Orthology (KO) [BR:ko00001]
 09100 Metabolism
  09109 Metabolism of terpenoids and polyketides
   01057 Biosynthesis of type II polyketide products
    K21297  ctcQ; flavin reductase (NADH)
   00253 Tetracycline biosynthesis
    K21297  ctcQ; flavin reductase (NADH)
Enzymes [BR:ko01000]
 1. Oxidoreductases
  1.5  Acting on the CH-NH group of donors
   1.5.1  With NAD+ or NADP+ as acceptor
    1.5.1.36  flavin reductase (NADH)
     K21297  ctcQ; flavin reductase (NADH)
BRITE hierarchy
Other DBs
COG: COG1853
GO: 0036382
Genes
MMI: MMAR_3634
MLI: MULP_03882
NSR: NS506_02368
SHY: SHJG_8629
SHO: SHJGH_8389
SVE: SVEN_0489 SVEN_6227
SDV: BN159_2477(pyr9)
SRC: M271_09870
SGU: SGLAU_04550
STRE: GZL_02226 GZL_02917
SLD: T261_7912
SRW: TUE45_00621(rbmH_1) TUE45_06418(rbmH_2)
SEN: SACE_4928
AOI: AORI_5335
ASE: ACPL_6145(ntaB)
AG: AEI98660(ctcQ)
 » show all
TaxonomyKoalaUniProt
Reference
  Authors
Zhu T, Cheng X, Liu Y, Deng Z, You D
  Title
Deciphering and engineering of the final step halogenase for improved chlortetracycline biosynthesis in industrial Streptomyces aureofaciens.
  Journal
Metab Eng 19:69-78 (2013)
DOI:10.1016/j.ymben.2013.06.003
  Sequence

KEGG   ENZYME: 1.14.19.49Help
Entry
EC 1.14.19.49               Enzyme                                 

Name
tetracycline 7-halogenase;
ctcP (gene name)
Class
Oxidoreductases;
Acting on paired donors, with incorporation or reduction of molecular oxygen;
With oxidation of a pair of donors resulting in the reduction of O2 to two molecules of water
BRITE hierarchy
Sysname
tetracycline:FADH2 oxidoreductase (7-halogenating)
Reaction(IUBMB)
tetracycline + FADH2 + chloride + O2 + H+ = 7-chlorotetracycline + FAD + 2 H2O [RN:R11478]
Reaction(KEGG)
Substrate
tetracycline [CPD:C06570];
FADH2 [CPD:C01352];
chloride [CPD:C00698];
O2 [CPD:C00007];
H+ [CPD:C00080]
Product
7-chlorotetracycline [CPD:C06571];
FAD [CPD:C00016];
H2O [CPD:C00001]
Comment
The enzyme, characterized from the bacterium Streptomyces aureofaciens, is a member of the flavin-dependent halogenase family. The enzyme forms a lysine chloramine intermediate on an internal lysine residue before transferring the chlorine to the substrate. It is stereo-selective for the 4S (natural) isomer of tetracycline. FADH2 is provided by a dedicated EC 1.5.1.36, flavin reductase (NADH).
History
EC 1.14.19.49 created 2016
Pathway
ec00253  Tetracycline biosynthesis
ec01057  Biosynthesis of type II polyketide products
ec01100  Metabolic pathways
ec01130  Biosynthesis of antibiotics
Orthology
K14257  tetracycline 7-halogenase / FADH2 O2-dependent halogenase
Genes
ENO: ECENHK_14345
ECLN: ECNIH4_08285
SRR: SerAS9_4266
SRL: SOD_c39980(prnC)
SRY: M621_21735
SPLY: Q5A_021590(soxA)
SRS: SerAS12_4267
SRA: SerAS13_4267
SMAF: D781_2599
SRZ: AXX16_2518
PAF: PAM18_2383(pltM)
PAEL: T223_13175
PFL: PFL_2784(pltM) PFL_3606(prnC)
PPRC: PFLCHA0_c28420(pltM) PFLCHA0_c36470(prnC)
PPRO: PPC_2829(pltM) PPC_3745(prnC)
PSEM: TO66_16625
CJA: CJA_2999(halA)
HCH: HCH_02500
BMA: BMAA1201(prnC)
BMV: BMASAVP1_0165(prnC)
BML: BMA10229_0442(prnC)
BMN: BMA10247_A1135(prnC)
BMAL: DM55_4314
BMAE: DM78_3855
BMAQ: DM76_3266
BMAI: DM57_4424
BMAF: DM51_4862
BMAZ: BM44_4276
BMAB: BM45_3400
BPS: BPSS1010
BTZ: BTL_5468
BTHA: DR62_5268
BOC: BG90_2527
BAM: Bamb_4728
BCON: NL30_32790
BUB: BW23_5780
BSEM: WJ12_18240
BMEC: WJ16_17190
MAB: MAB_2284
MABB: MASS_2208
MSTE: MSTE_02497
NNO: NONO_c51090(prnC)
SCO: SCO1275(2SCG18.22)
SCT: SCAT_5600
SVE: SVEN_0488
SFI: SFUL_3996
SAMB: SAM23877_1355(prnC)
FAL: FRAAL0926
SEN: SACE_4927
ASE: ACPL_6150
ACTS: ACWT_6018
CAI: Caci_3552
AMR: AM1_6083
CTHE: Chro_3657
RBA: RB1653(prnC)
RUL: UC8_31640
ABAS: ACPOL_5987
GBA: J421_4025
RMR: Rmar_2072
CPRV: CYPRO_2187
 » show all
Taxonomy
Reference
1  [PMID:7612997]
  Authors
Dairi T, Nakano T, Aisaka K, Katsumata R, Hasegawa M.
  Title
Cloning and nucleotide sequence of the gene responsible for chlorination of tetracycline.
  Journal
Biosci Biotechnol Biochem 59:1099-106 (1995)
DOI:10.1271/bbb.59.1099
  Sequence
Reference
2  [PMID:23800859]
  Authors
Zhu T, Cheng X, Liu Y, Deng Z, You D
  Title
Deciphering and engineering of the final step halogenase for improved chlortetracycline biosynthesis in industrial Streptomyces aureofaciens.
  Journal
Metab Eng 19:69-78 (2013)
DOI:10.1016/j.ymben.2013.06.003
  Sequence
Other DBs
ExplorEnz - The Enzyme Database: 1.14.19.49
IUBMB Enzyme Nomenclature: 1.14.19.49
ExPASy - ENZYME nomenclature database: 1.14.19.49
BRENDA, the Enzyme Database: 1.14.19.49

KEGG   REACTION: R11478Help
Entry
R11478                      Reaction                               

Name
tetracycline:FADH2 oxidoreductase (7-halogenating)
Definition
Tetracycline + FADH2 + Cl- + Oxygen + H+ <=> Chlortetracycline + FAD + 2 H2O
Equation
Reaction class
RC00949  C06570_C06571
Enzyme
Pathway
rn00253  Tetracycline biosynthesis
rn01057  Biosynthesis of type II polyketide products
rn01100  Metabolic pathways
rn01130  Biosynthesis of antibiotics
Module
M00823  Chlortetracycline biosynthesis, pretetramide => chlortetracycline
Orthology
K14257  tetracycline 7-halogenase / FADH2 O2-dependent halogenase [EC:1.14.19.49 1.14.19.-]
Other DBs
RHEA: 50715

DBGET integrated database retrieval system