CTCP_KITAU
ID CTCP_KITAU Reviewed; 555 AA.
AC A0A1E7MYN1; S4S3E1;
DT 25-APR-2018, integrated into UniProtKB/Swiss-Prot.
DT 18-JAN-2017, sequence version 1.
DT 03-AUG-2022, entry version 27.
DE RecName: Full=Tetracycline 7-halogenase {ECO:0000303|PubMed:23800859};
DE EC=1.14.19.49 {ECO:0000269|PubMed:23800859};
DE AltName: Full=FADH2-dependent halogenase {ECO:0000303|PubMed:23800859};
GN Name=ctcP {ECO:0000303|PubMed:23800859};
GN Synonyms=cts4 {ECO:0000303|PubMed:7612997};
GN ORFNames=B6264_18525 {ECO:0000312|EMBL:ARF80633.1},
GN HS99_0013305 {ECO:0000312|EMBL:OEV33529.1};
OS Kitasatospora aureofaciens (Streptomyces aureofaciens).
OC Bacteria; Actinobacteria; Streptomycetales; Streptomycetaceae;
OC Kitasatospora.
OX NCBI_TaxID=1894;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, CATALYTIC ACTIVITY,
RP BIOPHYSICOCHEMICAL PROPERTIES, DISRUPTION PHENOTYPE, SUBUNIT, SUBSTRATE
RP SPECIFICITY, AND REACTION MECHANISM.
RC STRAIN=F3 {ECO:0000312|EMBL:AEI98659.1};
RX PubMed=23800859; DOI=10.1016/j.ymben.2013.06.003;
RA Zhu T., Cheng X., Liu Y., Deng Z., You D.;
RT "Deciphering and engineering of the final step halogenase for improved
RT chlortetracycline biosynthesis in industrial Streptomyces aureofaciens.";
RL Metab. Eng. 19:69-78(2013).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 10762 / DSM 40127 / CCM 3239 / JCM 4008 / LMG 5968 / NBRC 12843
RC / NCIMB 8234 / A-377 {ECO:0000312|EMBL:OEV33529.1,
RC ECO:0000312|Proteomes:UP000037395};
RA Gradnigo J.S., Johnson N., Somerville G.A.;
RT "Sequencing, assembly and comparative genomics of S. aureofaciens ATCC
RT 10762.";
RL Submitted (AUG-2016) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=DM-1 {ECO:0000312|EMBL:ARF80633.1};
RA Hu H., Huang H., Min T.;
RT "TAR cloning and integrated overexpression of 6-demethylchlortetracycline
RT biosynthetic gene cluster in Streptomyces aureofaciens.";
RL Submitted (APR-2017) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP PATHWAY.
RC STRAIN=NRRL 3203;
RX PubMed=7612997; DOI=10.1271/bbb.59.1099;
RA Dairi T., Nakano T., Aisaka K., Katsumata R., Hasegawa M.;
RT "Cloning and nucleotide sequence of the gene responsible for chlorination
RT of tetracycline.";
RL Biosci. Biotechnol. Biochem. 59:1099-1106(1995).
CC -!- FUNCTION: Involved in the biosynthesis of chlorotetracycline (CTC), an
CC important member from antibiotics tetracycline (TC) family, which
CC inhibits protein synthesis in bacteria and is widely involved in
CC clinical therapy, animal feeds and aquaculture. Utilizes FADH(2)
CC supplied by the flavin reductase CtcQ, to catalyze the chlorination of
CC tetracycline (TC) at C7 position, leading to the production of 7-
CC chlorotetracycline. The enzyme forms a lysine chloramine intermediate
CC on an internal lysine residue before transferring the chlorine to the
CC substrate. It is stereo-selective for the 4S (natural) isomer of
CC tetracycline. {ECO:0000269|PubMed:23800859}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=chloride + FADH2 + O2 + tetracycline = 7-chlorotetracycline +
CC FAD + H(+) + 2 H2O; Xref=Rhea:RHEA:50712, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:17996,
CC ChEBI:CHEBI:57692, ChEBI:CHEBI:58307, ChEBI:CHEBI:77932,
CC ChEBI:CHEBI:133598; EC=1.14.19.49;
CC Evidence={ECO:0000269|PubMed:23800859};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=56 uM for tetracycline (TC) {ECO:0000269|PubMed:23800859};
CC Note=kcat is 0.51 min(-1) for tetracycline (TC) as substrate.
CC {ECO:0000269|PubMed:23800859};
CC -!- PATHWAY: Antibiotic biosynthesis. {ECO:0000305|PubMed:7612997}.
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:23800859}.
CC -!- DISRUPTION PHENOTYPE: Cells lacking this gene accumulate tetracycline
CC (TC) and abolishe the production of chlorotetracycline (CTC).
CC {ECO:0000269|PubMed:23800859}.
CC -!- SIMILARITY: Belongs to the flavin-dependent halogenase family.
CC Bacterial tryptophan halogenase subfamily. {ECO:0000305}.
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DR EMBL; HM627755; AEI98659.1; -; Genomic_DNA.
DR EMBL; JPRF03000065; OEV33529.1; -; Genomic_DNA.
DR EMBL; CP020567; ARF80633.1; -; Genomic_DNA.
DR RefSeq; WP_030282590.1; NZ_LBHA01000099.1.
DR RefSeq; WP_033348113.1; NZ_JNWR01000007.1.
DR AlphaFoldDB; A0A1E7MYN1; -.
DR SMR; A0A1E7MYN1; -.
DR STRING; 1894.JOER01000001_gene5209; -.
DR EnsemblBacteria; ARF80633; ARF80633; B6264_18525.
DR EnsemblBacteria; OEV33529; OEV33529; HS99_0013305.
DR KEGG; ag:AEI98659; -.
DR KEGG; kau:B6264_18525; -.
DR OMA; QYSASEC; -.
DR BRENDA; 1.14.19.49; 5978.
DR Proteomes; UP000037395; Unassembled WGS sequence.
DR GO; GO:0071949; F:FAD binding; IEA:InterPro.
DR GO; GO:0016491; F:oxidoreductase activity; IEA:UniProtKB-KW.
DR GO; GO:0017000; P:antibiotic biosynthetic process; IEA:UniProtKB-KW.
DR Gene3D; 3.50.50.60; -; 1.
DR InterPro; IPR002938; FAD-bd.
DR InterPro; IPR036188; FAD/NAD-bd_sf.
DR Pfam; PF01494; FAD_binding_3; 1.
DR SUPFAM; SSF51905; SSF51905; 1.
PE 1: Evidence at protein level;
KW Antibiotic biosynthesis; FAD; Flavoprotein; Oxidoreductase;
KW Reference proteome.
FT CHAIN 1..555
FT /note="Tetracycline 7-halogenase"
FT /id="PRO_0000443994"
FT BINDING 22..27
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000305|PubMed:23800859"
FT CONFLICT 480
FT /note="H -> R (in Ref. 1; AEI98659)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 555 AA; 62704 MW; 623595E650EBEB09 CRC64;
MTDTTADQTR HGDRPYDVVI IGSGLSGTML GSILAKHGFR IMLLDGAHHP RFAVGESTIG
QTLVVLRLIS DRYGVPEIAN LASFQDVLAN VSSSHGQKSN FGFMFHRDGE EPDPNETSQF
RIPSIVGNAA HFFRQDTDSY MFHAAVRYGC DARQYYRVEN IEFDDGGVTV SGADGSTVRA
RYLVDASGFR SPLARQLGLR EEPSRLKHHA RSIFTHMVGV DAIDDHVDTP AELRPPVPWN
DGTMHHIFER GWMWIIPFNN HPGATNPLCS VGIQLDERRY PARPDLTPEE EFWSHVDRFP
AVQRQLKGAR SVREWVRTDR MQYSSSRTVG ERWCLMSHAA GFIDPLFSRG LSNTCEIINA
LSWRLMAALR EDDFAVERFA YVEELEQGLL DWNDKLVNNS FISFSHYPLW NSVFRIWASA
SVIGGKRILN ALTRTKETGD DSHCQALDDN PYPGLWCPLD FYKEAFDELT ELCEAVDAGH
TTAEEAARVL EQRVRESDWM LPALGFNDPD THHINPTADK MIRIAEWATG HHRPEIRELL
AASAEEVRAA MRVKP
