KEGG   ORTHOLOGY: K14257
Entry
K14257                      KO                                     
Symbol
ctcP, cts4, prnC
Name
tetracycline 7-halogenase / FADH2 O2-dependent halogenase [EC:1.14.19.49 1.14.19.-]
Pathway
map00253  Tetracycline biosynthesis
map00404  Staurosporine biosynthesis
map01057  Biosynthesis of type II polyketide products
map01100  Metabolic pathways
map01110  Biosynthesis of secondary metabolites
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
 09180 Brite Hierarchies
  09181 Protein families: metabolism
   01008 Polyketide biosynthesis proteins
    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
Polyketide biosynthesis proteins [BR:ko01008]
 Polyketide tailoring proteins
  Halogenase
   K14257  ctcP, cts4, prnC; tetracycline 7-halogenase / FADH2 O2-dependent halogenase
Other DBs
RN: R11106 R11478
COG: COG0644
Genes
ECLN: ECNIH4_08285
ENO: ECENHK_14345
ECHG: FY206_15895
END: A4308_19035
ENZ: G0034_14940
SRR: SerAS9_4266
SRL: SOD_c39980(prnC)
SRY: M621_21735
SPLY: Q5A_021590(soxA)
SRS: SerAS12_4267
SMAF: D781_2599
PAF: PAM18_2383(pltM) PAM18_2389(pltD)
PFL: PFL_2784(pltM) PFL_2790(pltD) PFL_3606(prnC)
PPRO: PPC_2829(pltM) PPC_2835(pltD) 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
BSAV: WS86_22610
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)
NWL: NWFMUON74_24270(prnC)
SCO: SCO1275(2SCG18.22)
SCT: SCAT_5600
SVE: SVEN_0488
SFI: SFUL_3996
SAMB: SAM23877_1355(prnC)
FAL: FRAAL0926
SEN: SACE_4927
AORI: SD37_34235
ASE: ACPL_6150
ACTS: ACWT_6018
AMR: AM1_6083
CTHE: Chro_3657
RBA: RB1653(prnC)
RUL: UC8_31640
AHEL: Q31a_04260
FTJ: FTUN_8502
ABAS: ACPOL_5987
GBA: J421_4025
RMR: Rmar_2072
CPRV: CYPRO_2187
AG: AAB97506(prnC) AEI98659(ctcP) BAA07389(cts4)
 » show all
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)
DOI:10.1128/AEM.63.6.2147-2154.1997
  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: K21297
Entry
K21297                      KO                                     
Symbol
ctcQ
Name
flavin reductase (NADH) [EC:1.5.1.36]
Pathway
map00253  Tetracycline biosynthesis
map01057  Biosynthesis of type II polyketide products
map01100  Metabolic pathways
map01110  Biosynthesis of secondary metabolites
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)
 09180 Brite Hierarchies
  09181 Protein families: metabolism
   01008 Polyketide biosynthesis proteins
    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)
Polyketide biosynthesis proteins [BR:ko01008]
 Polyketide tailoring proteins
  Others
   K21297  ctcQ; flavin reductase (NADH)
Other DBs
COG: COG1853
GO: 0036382
Genes
MMI: MMAR_3634
MMAE: MMARE11_35420
MLI: MULP_03882
MPSE: MPSD_37010
MSHO: MSHO_33260
MMAG: MMAD_31880
NSR: NS506_02368
RKO: JWS14_38875
GJI: H1R19_00440
SHY: SHJG_8629
SDV: BN159_2477(pyr9)
SLD: T261_7912
SRW: TUE45_00621(rbmH_1) TUE45_06418(rbmH_2)
SNF: JYK04_01553(rbmH)
SHUN: DWB77_02860(rbmH)
SEN: SACE_4928
AOI: AORI_5335
AORI: SD37_34215
ASE: ACPL_6145(ntaB)
AG: AEI98660(ctcQ)
 » show all
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: 1.14.19.49
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
Sysname
tetracycline:FADH2 oxidoreductase (7-halogenating)
Reaction(IUBMB)
tetracycline + FADH2 + chloride + O2 + H+ = 7-chlorotetracycline + FAD + 2 H2O [RN:R11478]
Reaction(KEGG)
R11478
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
ec01110  Biosynthesis of secondary metabolites
Orthology
K14257  tetracycline 7-halogenase / FADH2 O2-dependent halogenase
Genes
ECLNECNIH4_08285
ENOECENHK_14345
ECHGFY206_15895
ENDA4308_19035
ENZG0034_14940
SRRSerAS9_4266
SRLSOD_c39980(prnC)
SRYM621_21735
SPLYQ5A_021590(soxA)
SRSSerAS12_4267
SRASerAS13_4267
SMAFD781_2599
SRZAXX16_2518
SERMCLM71_13480
SRHZFO014_20185
DYEEO087_02530
PAGPLES_25781 PLES_25851(pltD)
PAFPAM18_2383(pltM) PAM18_2389(pltD)
PAELT223_13175 T223_13210
PFLPFL_2784(pltM) PFL_2790(pltD) PFL_3606(prnC)
PPRCPFLCHA0_c28420(pltM) PFLCHA0_c28480(pltD) PFLCHA0_c36470(prnC)
PPROPPC_2829(pltM) PPC_2835(pltD) PPC_3745(prnC)
PCHEY04_18025
PCZPCL1606_28090
PCPJM49_15080
PSEMTO66_16625
CJACJA_2999(halA)
MMTMetme_1103
HCHHCH_02500
HAHEENC22_11335
ZPLZBT109_0564
BMABMAA1201(prnC)
BMVBMASAVP1_0165(prnC)
BMLBMA10229_0442(prnC)
BMNBMA10247_A1135(prnC)
BMALDM55_4314
BMAEDM78_3855
BMAQDM76_3266
BMAIDM57_4424
BMAFDM51_4862
BMAZBM44_4276
BMABBM45_3400
BPSBPSS1010
BPMBURPS1710b_A0003(prnC) BURPS1710b_A1117(prnC)
BPLBURPS1106A_A1397(halB) BURPS1106A_A2735
BPDBURPS668_A1482 BURPS668_A2887
BPSEBDL_4306 BDL_5424
BPSMBBQ_4119 BBQ_5121
BPSUBBN_4474 BBN_5477
BPSDBBX_4591 BBX_6149
BPZBP1026B_II1107
BPQBPC006_II1407 BPC006_II2698
BPKBBK_4753 BBK_6130
BPSHDR55_4322 DR55_5720
BPSABBU_3997 BBU_5014
BPSOX996_4250 X996_5524
BUTX994_5082 X994_6109
BTZBTL_5468
BTHADR62_5268
BOKDM82_2185 DM82_6304
BOCBG90_2527
BUUWS70_23845
BSAVWS86_22610
BURBcep18194_C6708
BCMBcenmc03_6985
BAMBamb_4728
BACBamMC406_5266
BCEPAPZ15_34530
BPYRABD05_31830
BCONNL30_32790
BUBBW23_5780
BSEMWJ12_18240
BMECWJ16_17190
BGDbgla_2g02310
BURKDM992_38825
MBDMEBOL_008076
SAMYDB32_006387
PIHUB51_18965
PCHIPC41400_07730
MABMAB_2284
MMVMYCMA_09365
MABBMASS_2208
MABLMMASJCM_2233
MIZBAB75_12200
MSTEMSTE_02497
NFRERS450000_00759
NCYNOCYR_5153
NBRO3I_018870
NNONONO_c51090(prnC)
NTPCRH09_09475 CRH09_09510
NOZDMB37_02795
NODFOH10_15045 FOH10_23420
NWLNWFMUON74_24270(prnC)
RRZCS378_19305
SCOSCO1275(2SCG18.22)
SSXSACTE_6340
SRCM271_09845
SCTSCAT_5600
SCYSCATT_55980
SVESVEN_0488
SDVBN159_0503 BN159_0504 BN159_2478 BN159_2479 BN159_2480 BN159_2482 BN159_2483(halB) BN159_2484
SFISFUL_3996
SLVSLIV_31415
SGUSGLAU_28900 SGLAU_28930
SAMBSAM23877_1355(prnC)
SCZABE83_16275
SPAVSpa2297_04645
SGSAVL59_19215
SCADDN051_32680
STRDNI25_18925 NI25_32825
SNZDC008_13265
SGDELQ87_03590
SVRCP971_23950
SFYGFH48_20345
SCAVCVT27_18180
SPACB1H29_04740 B1H29_31235
SCHACP983_36975
SCHFIPT68_15460
SFEUIM697_16645
SMOBJ7W19_30865
KAUB6264_18525
STRIC7M71_024630
ACTWF7P10_30225
FRAFrancci3_0437
FREFranean1_6189
FALFRAAL0926
SENSACE_4927
AORISD37_34235
SSYIEKG83_28905
ASEACPL_6150
ACTSACWT_6018
AIHAiant_03700
ACTRAsp14428_76420
PSUUPsuf_005050(prnC) Psuf_005170
CATICS0771_15270(prnC) CS0771_15280 CS0771_15290
DVCDvina_26625
CAICaci_3552 Caci_6353
AMRAM1_6083
CTHEChro_3657
CAPCLDAP_18670
CCZCCALI_00884
RBARB1653(prnC)
PIRVN12_12750
RULUC8_31640
ROLCA51_40950
AHELQ31a_04260
RLCK227x_49800
PLSVT03_06115
FMRFuma_06477
GMRGmarT_34080
GIMF1728_29395
GPNPan110_32210
MRIMal4_16350
GESVT84_18145
GMSSOIL9_20870
LRSPX52LOC_00381
FTJFTUN_8502
ULIETAA1_02960
ABASACPOL_5987
ADINH7849_12765
ABACLuPra_02345
GBAJ421_4025
RMRRmar_2072
RMGRhom172_0794
RBARAWN76_015905
MGINFRZ54_14670
CPRVCYPRO_2187
HLTI7X12_12635
HGIABY42_10695
HALEG3A49_13210
HLRHALLA_01030
 » show all
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: R11478
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
rn01110  Biosynthesis of secondary metabolites
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

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