TYLH1_STRFR
ID TYLH1_STRFR Reviewed; 420 AA.
AC Q9ZHQ1; Q9S4D6;
DT 07-JAN-2015, integrated into UniProtKB/Swiss-Prot.
DT 30-AUG-2017, sequence version 2.
DT 03-AUG-2022, entry version 90.
DE RecName: Full=20-oxo-5-O-mycaminosyltylactone 23-monooxygenase {ECO:0000305|PubMed:7283418};
DE EC=1.14.15.34 {ECO:0000305|PubMed:7283418};
DE AltName: Full=Cytochrome P-450 monooxygenase TylH1 {ECO:0000303|PubMed:10220165};
GN Name=tylH1 {ECO:0000303|PubMed:10220165};
GN Synonyms=tylHI {ECO:0000303|PubMed:10510490, ECO:0000312|EMBL:AAD41818.1};
OS Streptomyces fradiae (Streptomyces roseoflavus).
OC Bacteria; Actinobacteria; Streptomycetales; Streptomycetaceae;
OC Streptomyces.
OX NCBI_TaxID=1906;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=T59235;
RX PubMed=10510490; DOI=10.1038/sj.jim.2900707;
RA Bate N., Cundliffe E.;
RT "The mycinose-biosynthetic genes of Streptomyces fradiae, producer of
RT tylosin.";
RL J. Ind. Microbiol. Biotechnol. 23:118-122(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=ATCC 19609;
RX PubMed=10220165; DOI=10.1099/13500872-145-4-855;
RA Fouces R., Mellado E., Diez B., Barredo J.L.;
RT "The tylosin biosynthetic cluster from Streptomyces fradiae: genetic
RT organization of the left region.";
RL Microbiology 145:855-868(1999).
RN [3]
RP FUNCTION, CATALYTIC ACTIVITY, DISRUPTION PHENOTYPE, AND PATHWAY.
RX PubMed=7283418; DOI=10.1128/aac.20.2.214;
RA Baltz R.H., Seno E.T.;
RT "Properties of Streptomyces fradiae mutants blocked in biosynthesis of the
RT macrolide antibiotic tylosin.";
RL Antimicrob. Agents Chemother. 20:214-225(1981).
CC -!- FUNCTION: Involved in the biosynthesis of the complex macrolide
CC antibiotic tylosin. Catalyzes the hydroxylation of 20-oxo-5-O-beta-
CC mycaminosyltylactone at the C-23 position to yield 5-O-beta-
CC mycaminosyltylonolide. {ECO:0000269|PubMed:7283418}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=20-oxo-5-O-beta-D-mycaminosyltylonolide + 2 H(+) + O2 + 2
CC reduced [2Fe-2S]-[ferredoxin] = 5-O-beta-D-mycaminosyltylonolide +
CC H2O + 2 oxidized [2Fe-2S]-[ferredoxin]; Xref=Rhea:RHEA:24524,
CC Rhea:RHEA-COMP:10000, Rhea:RHEA-COMP:10001, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:33737,
CC ChEBI:CHEBI:33738, ChEBI:CHEBI:76803, ChEBI:CHEBI:76804;
CC EC=1.14.15.34; Evidence={ECO:0000305|PubMed:7283418};
CC -!- PATHWAY: Antibiotic biosynthesis; tylosin biosynthesis.
CC {ECO:0000269|PubMed:7283418}.
CC -!- DISRUPTION PHENOTYPE: Cells lacking this gene are blocked in the
CC monooxygenation of tylactone at position C-23 and accumulate 20-oxo-5-
CC O-beta-mycaminosyltylactone. {ECO:0000269|PubMed:7283418}.
CC -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAD41818.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AF147703; AAD41818.1; ALT_INIT; Genomic_DNA.
DR EMBL; AF055922; AAD12167.1; -; Genomic_DNA.
DR PDB; 6B11; X-ray; 1.99 A; A/B=1-420.
DR PDBsum; 6B11; -.
DR AlphaFoldDB; Q9ZHQ1; -.
DR SMR; Q9ZHQ1; -.
DR STRING; 1906.SFRA_26455; -.
DR PRIDE; Q9ZHQ1; -.
DR KEGG; ag:AAD12167; -.
DR eggNOG; COG2124; Bacteria.
DR BioCyc; MetaCyc:MON-18389; -.
DR BRENDA; 1.14.15.34; 5932.
DR UniPathway; UPA01018; -.
DR GO; GO:0020037; F:heme binding; IEA:InterPro.
DR GO; GO:0005506; F:iron ion binding; IEA:InterPro.
DR GO; GO:0004497; F:monooxygenase activity; IEA:UniProtKB-KW.
DR GO; GO:0016705; F:oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen; IEA:InterPro.
DR GO; GO:0017000; P:antibiotic biosynthetic process; IEA:UniProtKB-KW.
DR GO; GO:0016999; P:antibiotic metabolic process; IMP:UniProtKB.
DR Gene3D; 1.10.630.10; -; 1.
DR InterPro; IPR001128; Cyt_P450.
DR InterPro; IPR002397; Cyt_P450_B.
DR InterPro; IPR017972; Cyt_P450_CS.
DR InterPro; IPR036396; Cyt_P450_sf.
DR Pfam; PF00067; p450; 1.
DR PRINTS; PR00359; BP450.
DR PRINTS; PR00385; P450.
DR SUPFAM; SSF48264; SSF48264; 1.
DR PROSITE; PS00086; CYTOCHROME_P450; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Antibiotic biosynthesis; Heme; Iron; Metal-binding;
KW Monooxygenase; Oxidoreductase.
FT CHAIN 1..420
FT /note="20-oxo-5-O-mycaminosyltylactone 23-monooxygenase"
FT /id="PRO_0000431559"
FT REGION 1..28
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 118
FT /ligand="heme"
FT /ligand_id="ChEBI:CHEBI:30413"
FT /evidence="ECO:0000250|UniProtKB:P18326"
FT BINDING 122
FT /ligand="heme"
FT /ligand_id="ChEBI:CHEBI:30413"
FT /evidence="ECO:0000250|UniProtKB:P18326"
FT BINDING 311
FT /ligand="heme"
FT /ligand_id="ChEBI:CHEBI:30413"
FT /evidence="ECO:0000250|UniProtKB:P18326"
FT BINDING 367
FT /ligand="heme"
FT /ligand_id="ChEBI:CHEBI:30413"
FT /evidence="ECO:0000250|UniProtKB:P18326"
FT BINDING 369
FT /ligand="heme"
FT /ligand_id="ChEBI:CHEBI:30413"
FT /ligand_part="Fe"
FT /ligand_part_id="ChEBI:CHEBI:18248"
FT /note="axial binding residue"
FT /evidence="ECO:0000250|UniProtKB:P18326"
FT CONFLICT 136..137
FT /note="EL -> DV (in Ref. 2; AAD12167)"
FT /evidence="ECO:0000305"
FT STRAND 33..36
FT /evidence="ECO:0007829|PDB:6B11"
FT HELIX 48..55
FT /evidence="ECO:0007829|PDB:6B11"
FT STRAND 57..62
FT /evidence="ECO:0007829|PDB:6B11"
FT STRAND 68..72
FT /evidence="ECO:0007829|PDB:6B11"
FT HELIX 75..82
FT /evidence="ECO:0007829|PDB:6B11"
FT HELIX 91..93
FT /evidence="ECO:0007829|PDB:6B11"
FT TURN 99..104
FT /evidence="ECO:0007829|PDB:6B11"
FT STRAND 107..109
FT /evidence="ECO:0007829|PDB:6B11"
FT HELIX 110..112
FT /evidence="ECO:0007829|PDB:6B11"
FT HELIX 117..125
FT /evidence="ECO:0007829|PDB:6B11"
FT HELIX 126..128
FT /evidence="ECO:0007829|PDB:6B11"
FT HELIX 131..155
FT /evidence="ECO:0007829|PDB:6B11"
FT STRAND 157..160
FT /evidence="ECO:0007829|PDB:6B11"
FT HELIX 161..164
FT /evidence="ECO:0007829|PDB:6B11"
FT HELIX 166..178
FT /evidence="ECO:0007829|PDB:6B11"
FT HELIX 182..184
FT /evidence="ECO:0007829|PDB:6B11"
FT HELIX 185..195
FT /evidence="ECO:0007829|PDB:6B11"
FT HELIX 202..222
FT /evidence="ECO:0007829|PDB:6B11"
FT HELIX 230..240
FT /evidence="ECO:0007829|PDB:6B11"
FT HELIX 246..275
FT /evidence="ECO:0007829|PDB:6B11"
FT HELIX 279..287
FT /evidence="ECO:0007829|PDB:6B11"
FT HELIX 289..291
FT /evidence="ECO:0007829|PDB:6B11"
FT HELIX 292..303
FT /evidence="ECO:0007829|PDB:6B11"
FT STRAND 309..315
FT /evidence="ECO:0007829|PDB:6B11"
FT STRAND 317..319
FT /evidence="ECO:0007829|PDB:6B11"
FT STRAND 322..324
FT /evidence="ECO:0007829|PDB:6B11"
FT STRAND 329..332
FT /evidence="ECO:0007829|PDB:6B11"
FT HELIX 334..337
FT /evidence="ECO:0007829|PDB:6B11"
FT TURN 341..343
FT /evidence="ECO:0007829|PDB:6B11"
FT STRAND 344..346
FT /evidence="ECO:0007829|PDB:6B11"
FT HELIX 372..389
FT /evidence="ECO:0007829|PDB:6B11"
FT STRAND 408..410
FT /evidence="ECO:0007829|PDB:6B11"
FT STRAND 417..419
FT /evidence="ECO:0007829|PDB:6B11"
SQ SEQUENCE 420 AA; 45560 MW; 4C885311D5D30FF0 CRC64;
MSSSGDARPS QKGILLPAAR ANDTDEAAGR RSIAWPVART CPFSPPEQYA ALRAEEPIAR
AELWDGAPVW LISRQDHVRA LLADPRVSIH PAKLPRLSPS DGEAEASRSL LTLDPPDHGA
LRGHFIPEFG LRRVRELRPS VEQIVTGLLD DLTARGDEAD LLADFALPMA TQVICRLLDI
PYEDRDYFQE RTEQATRPAA GEEALEALLE LRDYLDRLIS GKTGRESGDG MLGSMVAQAR
GGGLSHADVL DNAVLLLAAG HETTASMVTM SVLVLLQHPT AWRELTVNPG LLPGAVDELL
RYLSIADGLR RSATADIEID GHTIRAGDGL VFLLAAANRD EAVFSEPEAF DIHRSARRHV
AFGYGPHQCL GQNLARMELE VALGAVLERL PALRPTTDVA GLRLKSDSAV FGVYELPVAW
