OXYL_STRRM
ID OXYL_STRRM Reviewed; 557 AA.
AC Q3S8Q4;
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:18422316};
DE AltName: Full=4-hydroxy-6-methylpretetramide 12a-monooxygenase {ECO:0000303|PubMed:18422316};
DE EC=1.14.13.233 {ECO:0000269|PubMed:18422316};
GN Name=oxyL {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 FUNCTION, CATALYTIC ACTIVITY, DISRUPTION PHENOTYPE, AND 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, 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 double hydroxylation of 6-
CC methylpretetramide to yield 4-keto-anhydrotetracycline, via the
CC insertion of oxygen atoms at the C-12a and C-4 positions of 6-
CC pretetramid. {ECO:0000269|PubMed:18422316,
CC 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:18422316};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=4-hydroxy-6-methylpretetramide + NADPH + O2 = 4-
CC dedimethylamino-4-oxo-anhydrotetracycline + H2O + NADP(+);
CC Xref=Rhea:RHEA:50356, ChEBI:CHEBI:15377, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:28464, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349,
CC ChEBI:CHEBI:132737; EC=1.14.13.233;
CC Evidence={ECO:0000269|PubMed:18422316};
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 are unable to produce the
CC tetracycline intermediate anhydrotetracycline (ATC).
CC {ECO:0000269|PubMed:18422316, ECO:0000269|PubMed:19472250}.
CC -!- MISCELLANEOUS: The OxyL-catalyzed conversion of 6-methylpretetramide to
CC 4-keto-anhydrotetracycline is incomplete, either due to low protein
CC expression levels and/or the slow reaction kinetics. Consequently, the
CC biosynthetic intermediate 4-hydroxyl-6-methylpretetramide can be
CC subjected to actions of endogenous enzymes that are not associated with
CC the pathway and lead to formation of shunt products. OxyE thus serves
CC as the ancillary enzyme to assist in the hydroxylation of C-4.
CC {ECO:0000305|PubMed:19472250}.
CC -!- SIMILARITY: Belongs to the PheA/TfdB FAD monooxygenase family.
CC {ECO:0000305}.
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DR EMBL; DQ143963; AAZ78335.1; -; Genomic_DNA.
DR RefSeq; WP_003981029.1; NZ_SADA01000149.1.
DR AlphaFoldDB; Q3S8Q4; -.
DR SMR; Q3S8Q4; -.
DR GeneID; 66859927; -.
DR KEGG; ag:AAZ78335; -.
DR OMA; QRMVPRM; -.
DR BRENDA; 1.14.13.232; 6084.
DR BRENDA; 1.14.13.233; 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; -; 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; Monooxygenase; NADP;
KW Oxidoreductase.
FT CHAIN 1..557
FT /note="6-methylpretetramide 4-monooxygenase"
FT /id="PRO_0000442357"
FT REGION 530..557
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 9..38
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000255"
FT BINDING 278..288
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000255"
SQ SEQUENCE 557 AA; 59624 MW; 15C4E3D5722E4F5A CRC64;
MPPEADGPQV LIAGAGPVGL TLAHELTRRR VRVRVIDRAD GPATTSRALA VHPRTLEACH
QMGLADALVA RGRPVVHFTV HLRGRQLIRF DTNYGRLPTA YPFSLMLDQV RTEEILRERL
AGLGVGIEWG VELADCAPCG DRVNAELRRD GRSEQVTVPW LVGADGSRST VRERLGLRLV
GDATQTWLNA DVVLDADLSR DSNHLVHTGS GTVLLVPFPD PGKWRAVDTG YAGQGADPET
VRRRLAGSLA RGLGRPVAVS EPTWVSVFRV QQRMITAMRS GRCFVAGDAA HVHSPASGQG
MNTGMQDAYN LAWKLADVVR GHAREELLDT YAAERIPVGG RLLSSTRTAT ALVALRNAVA
PVAMPVGLSF LKAVRPLKRR VEHRIMAGMS GLALHYADSP LTYGTGDGAA GVHPGHLVAC
TEQDVARHPG LRALRQALTD PRWLLLLFAD DGGAAELALR YGRAVQIRTV IPHEDEDGPA
LADPDDALRQ TLGVPPGGWA LIRPDGYLAA KGQRSGTTTL TARLQALHLL PEDTAPGAGD
SAGRPAPDGT RRGVTTE
