ID   OXYE_STRRM              Reviewed;         418 AA.
AC   Q3S8R0;
DT   22-NOV-2017, integrated into UniProtKB/Swiss-Prot.
DT   11-OCT-2005, sequence version 1.
DT   03-AUG-2022, entry version 49.
DE   RecName: Full=6-methylpretetramide 4-monooxygenase {ECO:0000303|PubMed:18422316};
DE            EC=1.14.13.232 {ECO:0000269|PubMed:19472250};
GN   Name=oxyE {ECO:0000303|PubMed:16597959};
OS   Streptomyces rimosus.
OC   Bacteria; Actinobacteria; Streptomycetales; Streptomycetaceae;
OC   Streptomyces.
OX   NCBI_TaxID=1927;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=16597959; DOI=10.1128/aem.72.4.2573-2580.2006;
RA   Zhang W., Ames B.D., Tsai S.C., Tang Y.;
RT   "Engineered biosynthesis of a novel amidated polyketide, using the
RT   malonamyl-specific initmguPCPB_SPHCRiation module from the oxytetracycline
RT   polyketide synthase.";
RL   Appl. Environ. Microbiol. 72:2573-2580(2006).
RN   [2]
RP   PATHWAY.
RX   PubMed=18422316; DOI=10.1021/ja800951e;
RA   Zhang W., Watanabe K., Cai X., Jung M.E., Tang Y., Zhan J.;
RT   "Identifying the minimal enzymes required for anhydrotetracycline
RT   biosynthesis.";
RL   J. Am. Chem. Soc. 130:6068-6069(2008).
RN   [3]
RP   FUNCTION, CATALYTIC ACTIVITY, AND DISRUPTION PHENOTYPE.
RC   STRAIN=ATCC 10970;
RX   PubMed=19472250; DOI=10.1002/cbic.200900122;
RA   Wang P., Zhang W., Zhan J., Tang Y.;
RT   "Identification of OxyE as an ancillary oxygenase during tetracycline
RT   biosynthesis.";
RL   ChemBioChem 10:1544-1550(2009).
CC   -!- FUNCTION: Involved in the biosynthesis of the tetracycline antibiotic,
CC       oxytetracycline. Catalyzes the C-4 hydroxylation of 6-
CC       methylpretetramide to yield the intermediate 4-hydroxyl-6-
CC       methylpretetramid, which is subsequently hydroxylated by OxyL to yield
CC       4-keto-anhydrotetracycline. OxyE serves as the ancillary enzyme to
CC       assist OxyL in the hydroxylation of C-4. {ECO:0000269|PubMed:19472250}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=6-methylpretetramide + 2 H(+) + NADPH + O2 = 4-hydroxy-6-
CC         methylpretetramide + H2O + NADP(+); Xref=Rhea:RHEA:50008,
CC         ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC         ChEBI:CHEBI:28464, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349,
CC         ChEBI:CHEBI:132734; EC=1.14.13.232;
CC         Evidence={ECO:0000269|PubMed:19472250};
CC   -!- COFACTOR:
CC       Name=FAD; Xref=ChEBI:CHEBI:57692;
CC         Evidence={ECO:0000250|UniProtKB:P42535};
CC   -!- PATHWAY: Antibiotic biosynthesis; oxytetracycline biosynthesis.
CC       {ECO:0000305|PubMed:18422316}.
CC   -!- DISRUPTION PHENOTYPE: Cells lacking this gene produce oxytetracycline
CC       with a yield of only 50% compared to the wild-type.
CC       {ECO:0000269|PubMed:19472250}.
CC   -!- SIMILARITY: Belongs to the PheA/TfdB FAD monooxygenase family.
CC       {ECO:0000305}.
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DR   EMBL; DQ143963; AAZ78329.1; -; Genomic_DNA.
DR   RefSeq; WP_003981023.1; NZ_SADA01000149.1.
DR   AlphaFoldDB; Q3S8R0; -.
DR   SMR; Q3S8R0; -.
DR   PRIDE; Q3S8R0; -.
DR   GeneID; 66859933; -.
DR   KEGG; ag:AAZ78329; -.
DR   OMA; TLPHKGY; -.
DR   BRENDA; 1.14.13.232; 6084.
DR   UniPathway; UPA00926; -.
DR   GO; GO:0071949; F:FAD binding; IEA:InterPro.
DR   GO; GO:0004497; F:monooxygenase activity; IEA:UniProtKB-KW.
DR   GO; GO:0017000; P:antibiotic biosynthetic process; IEA:UniProtKB-KW.
DR   Gene3D; 3.50.50.60; -; 2.
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; Monooxygenase; NADP;
KW   Oxidoreductase.
FT   CHAIN           1..418
FT                   /note="6-methylpretetramide 4-monooxygenase"
FT                   /id="PRO_0000442356"
FT   BINDING         15..44
FT                   /ligand="FAD"
FT                   /ligand_id="ChEBI:CHEBI:57692"
FT                   /evidence="ECO:0000255"
FT   BINDING         289..299
FT                   /ligand="FAD"
FT                   /ligand_id="ChEBI:CHEBI:57692"
FT                   /evidence="ECO:0000255"
SQ   SEQUENCE   418 AA;  45622 MW;  0AD8525E0C2FD1B8 CRC64;
     MTGHPRPPAD GAHTDVCVVG GGPAGLTLAL LMLRSGARVT LVERSRSLDR AYRGEILQPG
     GQALLDALGV LEGARRRGCH EHDGFRLEER GRTLINGDYR RLPGPYNCLL SLPQQHLLTD
     LLERCRAHPR FTCLTGTKVN GLVEEGGVVR GVVCGGGADG LVVRADCVVG ADGRYSTVRK
     LAGIPYDRIE LFDQDVLWCK LTAPATRTVR IFRAGGNPVL AYTSFPDCVQ LGWTLPHKGY
     QALAERGFAH VKERIRAAVP EYADTVDQQL NSFKDVSLLD VFAGSARRWA RDGLLLIGDS
     AHTHSPIGAQ GINLAIQDAV AAHPVLCEGL RRRDLSERFL DAVAARRRPE TERATRVQVM
     QSRMMLSTGR VSAAVRPKAA MLVSRTPAYR SVLRRIAYGD QTLRVRSDLF EEGEPATV