DNRF_STRC0
ID DNRF_STRC0 Reviewed; 489 AA.
AC P72495;
DT 19-MAR-2014, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-1997, sequence version 2.
DT 03-AUG-2022, entry version 93.
DE RecName: Full=Aklavinone 12-hydroxylase DnrF;
DE EC=1.14.13.180;
DE AltName: Full=Aklavinone 11-hydroxylase;
GN Name=dnrF;
OS Streptomyces peucetius subsp. caesius.
OC Bacteria; Actinobacteria; Streptomycetales; Streptomycetaceae;
OC Streptomyces.
OX NCBI_TaxID=55158;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, CATALYTIC ACTIVITY, AND
RP DISRUPTION PHENOTYPE.
RC STRAIN=ATCC 27952 / DSM 41231 / NBRC 14660 / 106FI;
RX PubMed=7961477; DOI=10.1128/jb.176.22.7096-7101.1994;
RA Hong Y.S., Hwang C.K., Hong S.K., Kim Y.H., Lee J.J.;
RT "Molecular cloning and characterization of the aklavinone 11-hydroxylase
RT gene of Streptomyces peucetius subsp. caesius ATCC 27952.";
RL J. Bacteriol. 176:7096-7101(1994).
CC -!- FUNCTION: Involved in the biosynthesis of the anthracyclines
CC carminomycin, rhodomycin, daunorubicin (daunomycin) and doxorubicin
CC (adriamycin) which are aromatic polyketide antibiotics that exhibit
CC high cytotoxicity and are widely applied in the chemotherapy of a
CC variety of cancers. Catalyzes the incorporation of a hydroxyl group at
CC position C-11 of aklavinone, resulting in epsilon-rhodomycinone.
CC {ECO:0000269|PubMed:7961477}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=aklavinone + H(+) + NADPH + O2 = epsilon-rhodomycinone + H2O +
CC NADP(+); Xref=Rhea:RHEA:37835, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:31181, ChEBI:CHEBI:57783,
CC ChEBI:CHEBI:58349, ChEBI:CHEBI:75291; EC=1.14.13.180;
CC Evidence={ECO:0000269|PubMed:7961477};
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692; Evidence={ECO:0000250};
CC -!- PATHWAY: Antibiotic biosynthesis; daunorubicin biosynthesis.
CC -!- PATHWAY: Antibiotic biosynthesis; carminomycin biosynthesis.
CC -!- PATHWAY: Antibiotic biosynthesis; rhodomycin biosynthesis.
CC -!- PATHWAY: Antibiotic biosynthesis; doxorubicin biosynthesis.
CC -!- SUBUNIT: Monomer. {ECO:0000250}.
CC -!- DISRUPTION PHENOTYPE: Cells lacking this gene do not produce epsilon-
CC rhodomycinone and accumulate 11-deoxycarminomycin and 11-
CC deoxydaunorubicin. {ECO:0000269|PubMed:7961477}.
CC -!- MISCELLANEOUS: S.peucetius subsp. caesius ATCC 27952, a mutant strain
CC derived from S.peucetius ATCC 29050, is the only organism reported to
CC produce doxorubicin in vivo (PubMed:7961477).
CC {ECO:0000305|PubMed:7961477}.
CC -!- SIMILARITY: Belongs to the PheA/TfdB FAD monooxygenase family.
CC {ECO:0000305}.
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DR EMBL; U09844; AAA62496.1; -; Genomic_DNA.
DR AlphaFoldDB; P72495; -.
DR SMR; P72495; -.
DR BioCyc; MetaCyc:MON-18175; -.
DR BRENDA; 1.14.13.180; 6073.
DR UniPathway; UPA00054; -.
DR UniPathway; UPA01040; -.
DR UniPathway; UPA01041; -.
DR UniPathway; UPA01042; -.
DR GO; GO:0071949; F:FAD binding; ISS:UniProtKB.
DR GO; GO:0016709; F:oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, NAD(P)H as one donor, and incorporation of one atom of oxygen; IDA:UniProtKB.
DR GO; GO:1901771; P:daunorubicin biosynthetic process; IDA:UniProtKB.
DR GO; GO:0044598; P:doxorubicin metabolic process; IDA:UniProtKB.
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; NAD; NADP; Nucleotide-binding;
KW Oxidoreductase.
FT CHAIN 1..489
FT /note="Aklavinone 12-hydroxylase DnrF"
FT /id="PRO_0000425677"
FT REGION 402..428
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 402..421
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 224
FT /note="Proton acceptor"
FT /evidence="ECO:0000250"
FT BINDING 17..18
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250"
FT BINDING 37
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250"
FT BINDING 121
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250"
FT BINDING 145
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250"
FT BINDING 308
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250"
FT BINDING 317
FT /ligand="aklavinone"
FT /ligand_id="ChEBI:CHEBI:31181"
FT /evidence="ECO:0000250"
SQ SEQUENCE 489 AA; 52324 MW; 6050032A6DC2EA28 CRC64;
MALTKPDVDV LVVGGGLGGL STALFLARRG ARVLLVERHA STSVLPKAAG QNPRTMELFR
FGGVADEILA TDDIRGAQGD FTIKVVERVG GRVPAQLRES FEELVGATEQ CTPMPWALAP
QDRVEPVLVA HAAKHGAEIR FATELTSFQA GDDGVTARLR DLGTGAESTV SARYLVAADG
PRSAIRESLG ITRHGHGTLA HFMGVIFEAD LTAVVPPGST GWYYLQHPDF TGTFGPTDRP
NRHTFYVRYD PERGERPEDY TPQRCTELIR LAVDAPGLVP DILDIQAWDM AAYIADRWRE
GPVLLVGDAA KVTPPTGGMG GNTAIGHGFD VAWKLAAVLR GEAGERLLDS YGADGSLVSR
LVVDESLAIY AQRMAPHLLG SVPEERGTAQ VVLGFRYRST AVAAEDDDPE PTEDPRRPSG
RPGFRAPHVW IEQDGTRRST VELFGDCWVL LAAPEGGAWG QAAARAARIW ASASTSISSA
AMSPPPPAN
