KEGG ENZYME: 1.14.19.49

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

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

SRA:	SerAS13_4267

SMAF:

D781_2599

SRZ:	AXX16_2518

SERM:

CLM71_13480

SRHZ:

FO014_20185

DYE:	EO087_02530

PAG:	PLES_25781 PLES_25851(pltD)

PAF:	PAM18_2383(pltM) PAM18_2389(pltD)

PAEL:

T223_13175 T223_13210

PFL:	PFL_2784(pltM) PFL_2790(pltD) PFL_3606(prnC)

PPRC:

PFLCHA0_c28420(pltM) PFLCHA0_c28480(pltD) PFLCHA0_c36470(prnC)

PPRO:

PPC_2829(pltM) PPC_2835(pltD) PPC_3745(prnC)

PCH:	EY04_18025

PCZ:	PCL1606_28090

PCP:	JM49_15080

PSEM:

TO66_16625

PPII:

QL104_13925 QL104_13955 QL104_19155 QL104_23510

CJA:	CJA_2999(halA)

MMT:	Metme_1103

HCH:

HCH_02500

HAHE:

ENC22_11335

HAHH:

O5O45_06390

ZPL:	ZBT109_0564

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

BPM:	BURPS1710b_A0003(prnC) BURPS1710b_A1117(prnC)

BPL:	BURPS1106A_A1397(halB) BURPS1106A_A2735

BPD:	BURPS668_A1482 BURPS668_A2887

BPSE:

BDL_4306 BDL_5424

BPSM:

BBQ_4119 BBQ_5121

BPSU:

BBN_4474 BBN_5477

BPSD:

BBX_4591 BBX_6149

BPZ:	BP1026B_II1107

BPQ:	BPC006_II1407 BPC006_II2698

BPK:	BBK_4753 BBK_6130

BPSH:

DR55_4322 DR55_5720

BPSA:

BBU_3997 BBU_5014

BPSO:

X996_4250 X996_5524

BUT:	X994_5082 X994_6109

BTZ:

BTL_5468

BTHA:

DR62_5268

BOK:	DM82_2185 DM82_6304

BOC:

BG90_2527

BUU:	WS70_23845

BSAV:

WS86_22610

BUR:	Bcep18194_C6708

BCM:	Bcenmc03_6985

BAM:

Bamb_4728

BAC:	BamMC406_5266

BCEP:

APZ15_34530

BPYR:

ABD05_31830

BCON:

NL30_32790

BUB:

BW23_5780

BSEM:

WJ12_18240

BMEC:

WJ16_17190

BARI:

NLX30_39210

BGD:	bgla_2g02310

BURK:

DM992_38825

MBD:	MEBOL_008076

SAMY:

DB32_006387

NANN:

O0S08_14700

PIH:	UB51_18965

PCHI:

PC41400_07730

MAB:

MAB_2284

MMV:	MYCMA_09365

MABB:

MASS_2208

MABL:

MMASJCM_2233

MIZ:	BAB75_12200

MSTE:

MSTE_02497

NFR:	ERS450000_00759

NCY:	NOCYR_5153

NBR:	O3I_018870

NNO:	NONO_c51090(prnC)

NTP:	CRH09_09475 CRH09_09510

NOZ:	DMB37_02795

NOD:	FOH10_15045 FOH10_23420

NWL:	NWFMUON74_24270(prnC)

RRZ:	CS378_19305

SCO:	SCO1275(2SCG18.22)

SFI:

SFUL_3996

SSX:	SACTE_6340

SRC:	M271_09845

SVE:

SVEN_0488

SDV:	BN159_0503 BN159_0504 BN159_2478 BN159_2479 BN159_2480 BN159_2482 BN159_2483(halB) BN159_2484

SLV:	SLIV_31415

SGU:	SGLAU_28900 SGLAU_28930

SAMB:

SAM23877_1355(prnC)

SCZ:	ABE83_16275

SPAV:

Spa2297_04645

SGS:	AVL59_19215

SCAD:

DN051_32680

SPHW:

NFX46_19280

STRD:

NI25_18925 NI25_32825

SNZ:	DC008_13265

SGD:	ELQ87_03590

SVR:	CP971_23950

SFY:	GFH48_20345

SCAV:

CVT27_18180

SPAC:

B1H29_04740 B1H29_31235

SCHA:

CP983_36975

SCHF:

IPT68_15460

SFEU:

IM697_16645

SMOB:

J7W19_30865

SCIR:

STRCI_006110 STRCI_006112 STRCI_006113 STRCI_006114 STRCI_007874 STRCI_007875

STUD:

STRTU_005058

SCT:

SCAT_5600

SCY:	SCATT_55980

KAU:	B6264_18525

STRI:

C7M71_024630

ABRY:

NYE86_15915 NYE86_16955

ACTW:

F7P10_30225

SPIQ:

OHA34_06380

ACTQ:

OG417_42950

FRA:	Francci3_0437

FRE:	Franean1_6189

FAL:

FRAAL0926

SEN:

SACE_4927

AORI:

SD37_34235

SSYI:

EKG83_28905

KBU:	Q4V64_07440

ASE:

ACPL_6150

ACTS:

ACWT_6018

AIH:	Aiant_03700

ACTR:

Asp14428_76420

ACTL:

L3i22_052610

AOU:	ACTOB_004306 ACTOB_005290

PSUU:

Psuf_005050(prnC) Psuf_005170

CATI:

CS0771_15270(prnC) CS0771_15280 CS0771_15290

DVC:	Dvina_26625

DAUR:

Daura_27000 Daura_37810

DMAT:

Dmats_22070

CAI:	Caci_3552 Caci_6353

AMR:

AM1_6083

CTHE:

Chro_3657

CAP:	CLDAP_18670

CCZ:	CCALI_00884

RBA:	RB1653(prnC)

PIR:	VN12_12750

RUL:

UC8_31640

ROL:	CA51_40950

RUV:

EC9_43150

AHEL:

Q31a_04260

RLC:	K227x_49800

SMAM:

Mal15_37510

SNEP:

Enr13x_29450

PLS:	VT03_06115

FMR:	Fuma_06477

GMR:	GmarT_34080

GIM:	F1728_29395

GPN:	Pan110_32210

GFM:	Enr17x_33880

MRI:	Mal4_16350

ACAF:

CA12_04690

PVAR:

SH412_004361

CCOP:

Mal65_29530

GES:	VT84_18145

GMS:	SOIL9_20870

LRS:	PX52LOC_00381

FTJ:

FTUN_8502

ULI:	ETAA1_02960

ABAS:

ACPOL_5987

ADIN:

H7849_12765

ABAC:

LuPra_02345

GBA:

J421_4025

THEO:

IMW88_05220

MGIN:

FRZ54_14670

RMR:

Rmar_2072

RMG:	Rhom172_0794

RLO:	GQ464_016890

RBAR:

AWN76_015905

CPRV:

CYPRO_2187

HLT:	I7X12_12635

HGI:	ABY42_10695

HALE:

G3A49_13210

HLR:	HALLA_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

[ag:BAA07389]

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

[ag:AEI98659 AEI98660]

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

DBGET integrated database retrieval system