DNRF_STRPE
ID DNRF_STRPE Reviewed; 489 AA.
AC P32009; P72497;
DT 01-JUL-1993, integrated into UniProtKB/Swiss-Prot.
DT 19-MAR-2014, sequence version 2.
DT 03-AUG-2022, entry version 66.
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.
OC Bacteria; Actinobacteria; Streptomycetales; Streptomycetaceae;
OC Streptomyces.
OX NCBI_TaxID=1950;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, CATALYTIC ACTIVITY, AND
RP SUBSTRATE SPECIFICITY.
RC STRAIN=ATCC 29050 / DSM 40754 / JCM 9920 / NBRC 100596 / NCIMB 10972;
RX PubMed=7773378; DOI=10.1099/13500872-141-4-1007;
RA Filippini S., Solinas M.M., Breme U., Schluter M.B., Gabellini D.,
RA Biamonti G., Colombo A.L., Garofano L.;
RT "Streptomyces peucetius daunorubicin biosynthesis gene, dnrF: sequence and
RT heterologous expression.";
RL Microbiology 141:1007-1016(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-79.
RC STRAIN=ATCC 29050 / DSM 40754 / JCM 9920 / NBRC 100596 / NCIMB 10972;
RX PubMed=1924314; DOI=10.1073/pnas.88.19.8553;
RA Guilfoile P.G., Hutchinson C.R.;
RT "A bacterial analog of the mdr gene of mammalian tumor cells is present in
RT Streptomyces peucetius, the producer of daunorubicin and doxorubicin.";
RL Proc. Natl. Acad. Sci. U.S.A. 88:8553-8557(1991).
CC -!- FUNCTION: Involved in the biosynthesis of the anthracyclines
CC carminomycin, rhodomycin and daunorubicin (daunomycin) which are
CC aromatic polyketide antibiotics that exhibit high cytotoxicity and are
CC widely applied in the chemotherapy of a variety of cancers. Catalyzes
CC the incorporation of a hydroxyl group at position C-11 of aklavinone,
CC resulting in epsilon-rhodomycinone. It cannot accept substrates
CC glycosylated at position C-7. It can also hydroxylate 11-
CC deoxycarminomycinone and can use both NAD or NADP.
CC {ECO:0000269|PubMed:7773378}.
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:7773378};
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 -!- SUBUNIT: Monomer. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the PheA/TfdB FAD monooxygenase family.
CC {ECO:0000305}.
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DR EMBL; U18082; AAC43342.1; -; Genomic_DNA.
DR EMBL; M73758; AAA74716.1; -; Genomic_DNA.
DR PIR; S27706; S27706.
DR AlphaFoldDB; P32009; -.
DR SMR; P32009; -.
DR KEGG; ag:AAC43342; -.
DR BRENDA; 1.14.13.180; 6073.
DR UniPathway; UPA00054; -.
DR UniPathway; UPA01040; -.
DR UniPathway; UPA01042; -.
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; NAD; NADP; Nucleotide-binding;
KW Oxidoreductase.
FT CHAIN 1..489
FT /note="Aklavinone 12-hydroxylase DnrF"
FT /id="PRO_0000425676"
FT REGION 402..428
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 455..489
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; 52317 MW; 5BBE25F0974B34EE CRC64;
MALTKPDVDV LVVGGGLGGL STALFLARRG ARVLLVERHA STSVLPKAAG QNPRTMELFR
FGGVADEILA TDDIRGAQGD FTIKVVERVG GRVLHSFAES FEELVGATEQ CTPMPWALAP
QDRVEPVLVA HAAKHGAEIR FATELTSFQA GDDGVTARLR DLGTGAESTV SARYLVAADG
PRSAIRESLG ITRHGHGTLA HFMGVIFEAD LTAVVPPGST GWYYLQHPDF TGTFGPTDRP
NRHTFYVATT PERGERPEDY TPQRCTELIR LAVDAPGLVP DILDIQAWDM AAYIADRWRE
GPVLLVGDAA KVTPPTGGMG GNTAIGDGFD VAWKLAAVLR GEAGERLLDS YGAERSLVSR
LVVDESLAIY AQRMAPHLLG SVPEERGTAQ VVLGFRYRST AVAAEDDDPE PTEDPRRPSG
RPGFRAPHVW IEQDGTRRST VELFGDCWVL LAAPEGGAWP GRPPAPPRIW ASASTSISSA
AMSPPPPAN
