ID   APF7_GIBF5              Reviewed;         530 AA.
AC   S0DPM1;
DT   07-SEP-2016, integrated into UniProtKB/Swiss-Prot.
DT   18-SEP-2013, sequence version 1.
DT   26-FEB-2020, entry version 23.
DE   RecName: Full=Cytochrome P450 monooxygenase apf7 {ECO:0000303|PubMed:25058475};
DE            EC=1.-.-.- {ECO:0000305|PubMed:25058475};
DE   AltName: Full=Apicidin F synthesis protein 7 {ECO:0000303|PubMed:25058475};
GN   Name=apf7 {ECO:0000303|PubMed:25058475}; ORFNames=FFUJ_00007;
OS   Gibberella fujikuroi (strain CBS 195.34 / IMI 58289 / NRRL A-6831) (Bakanae
OS   and foot rot disease fungus) (Fusarium fujikuroi).
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Sordariomycetes;
OC   Hypocreomycetidae; Hypocreales; Nectriaceae; Fusarium;
OC   Fusarium fujikuroi species complex.
OX   NCBI_TaxID=1279085;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=CBS 195.34 / IMI 58289 / NRRL A-6831;
RX   PubMed=23825955; DOI=10.1371/journal.ppat.1003475;
RA   Wiemann P., Sieber C.M.K., von Bargen K.W., Studt L., Niehaus E.-M.,
RA   Espino J.J., Huss K., Michielse C.B., Albermann S., Wagner D.,
RA   Bergner S.V., Connolly L.R., Fischer A., Reuter G., Kleigrewe K., Bald T.,
RA   Wingfield B.D., Ophir R., Freeman S., Hippler M., Smith K.M., Brown D.W.,
RA   Proctor R.H., Muensterkoetter M., Freitag M., Humpf H.-U., Gueldener U.,
RA   Tudzynski B.;
RT   "Deciphering the cryptic genome: genome-wide analyses of the rice pathogen
RT   Fusarium fujikuroi reveal complex regulation of secondary metabolism and
RT   novel metabolites.";
RL   PLoS Pathog. 9:E1003475-E1003475(2013).
RN   [2]
RP   FUNCTION, AND BIOTECHNOLOGY.
RX   PubMed=24195442; DOI=10.1021/np4006053;
RA   von Bargen K.W., Niehaus E.M., Bergander K., Brun R., Tudzynski B.,
RA   Humpf H.U.;
RT   "Structure elucidation and antimalarial activity of apicidin F: an
RT   apicidin-like compound produced by Fusarium fujikuroi.";
RL   J. Nat. Prod. 76:2136-2140(2013).
RN   [3]
RP   FUNCTION, AND INDUCTION.
RX   PubMed=25058475; DOI=10.1371/journal.pone.0103336;
RA   Niehaus E.M., Janevska S., von Bargen K.W., Sieber C.M., Harrer H.,
RA   Humpf H.U., Tudzynski B.;
RT   "Apicidin F: characterization and genetic manipulation of a new secondary
RT   metabolite gene cluster in the rice pathogen Fusarium fujikuroi.";
RL   PLoS ONE 9:E103336-E103336(2014).
CC   -!- FUNCTION: Cytochrome P450 monooxygenase; part of the gene cluster that
CC       mediates the biosynthesis of the cyclic tetrapeptide apicidin F (APF)
CC       (PubMed:25058475). The non-ribosomal peptide synthetase apf1
CC       incorporates four different amino acids to produce apicidin F: L-
CC       phenylalanine, D-pipecolic acid (D-pip), N-methoxy-L-tryptophan and L-
CC       2-aminooctanedioic acid (PubMed:25058475). L-Phenylalanine is the only
CC       proteinogenic amino acid directly used by apf1 (PubMed:24195442,
CC       PubMed:25058475). The 3 other apf1 substrates are non-proteinogenic and
CC       have to be modified by other enzymes of the cluster (PubMed:25058475).
CC       Lysine is converted to delta-1-pyrroline-5-carboxylate (P5C) which is
CC       reduced to L-pipecolic acid (L-pip) by apf3 (PubMed:25058475). L-pip is
CC       epimerized to D-pip, probably by apf1 activity, prior to incorporation
CC       (PubMed:25058475). L-Tryptophan is N-oxidyzed by one of the cytochrome
CC       P450 monooxygenases (apf7 or apf8), and further methylated at the
CC       hydroxy group by the O-methyltransferase apf6 to yield N-methoxy-L-
CC       tryptophan (PubMed:25058475). The synthesis of the fourth apf1
CC       substrate is more complex (PubMed:25058475). The fatty acid synthase
CC       apf5 is involved in the synthesis of the octanoic acid backbone of L-2-
CC       aminooctanedioic acid by fixing one acetyl-CoA unit and three malonyl-
CC       CoA units (PubMed:25058475). Then one of the cytochrome P450
CC       monooxygenases (apf7 or apf8) may oxidize this backbone to 2-
CC       oxooctanoic acid (PubMed:25058475). The aminotransferase apf4 is
CC       predicted to catalyze the exchange of the keto group with an amino
CC       group (PubMed:25058475). The next step would be the oxidation of 2-
CC       aminooctanoic acid by one of the cytochrome P450 monooxygenases (apf7
CC       or apf8). The last step is the oxidation of 2-amino-8-hydroxyoctanoic
CC       acid to 2-aminooctanedioic acid is catalyzed by the FAD-dependent
CC       monooxygenase apf9 (PubMed:25058475). {ECO:0000269|PubMed:24195442,
CC       ECO:0000269|PubMed:25058475}.
CC   -!- COFACTOR:
CC       Name=heme; Xref=ChEBI:CHEBI:30413;
CC         Evidence={ECO:0000250|UniProtKB:P04798};
CC   -!- PATHWAY: Secondary metabolite biosynthesis.
CC       {ECO:0000269|PubMed:25058475}.
CC   -!- SUBCELLULAR LOCATION: Membrane {ECO:0000255}; Single-pass membrane
CC       protein {ECO:0000255}.
CC   -!- INDUCTION: Expression is positively regulated by the apicidin F
CC       cluster-specific transcription factor apf2 that binds to the eight-
CC       base-pair motif 5'-TGACGTGA-3' called the 'Api-box' that is found in
CC       all promoters of the apicidin F cluster except in the promoter region
CC       of apf2 itself (PubMed:25058475). {ECO:0000269|PubMed:25058475}.
CC   -!- BIOTECHNOLOGY: Apicidin F, like the other known apicidins, is a cyclic
CC       tetrapeptides with anti-malarial properties via histone deacetylase
CC       inhibitory activity (PubMed:24195442). {ECO:0000269|PubMed:24195442}.
CC   -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
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DR   EMBL; HF679023; CCT63357.1; -; Genomic_DNA.
DR   EnsemblFungi; CCT63357; CCT63357; FFUJ_00007.
DR   HOGENOM; CLU_001570_14_11_1; -.
DR   Proteomes; UP000016800; Chromosome 1.
DR   GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
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   Gene3D; 1.10.630.10; -; 1.
DR   InterPro; IPR001128; Cyt_P450.
DR   InterPro; IPR017972; Cyt_P450_CS.
DR   InterPro; IPR002401; Cyt_P450_E_grp-I.
DR   InterPro; IPR036396; Cyt_P450_sf.
DR   Pfam; PF00067; p450; 1.
DR   PRINTS; PR00463; EP450I.
DR   PRINTS; PR00385; P450.
DR   SUPFAM; SSF48264; SSF48264; 1.
DR   PROSITE; PS00086; CYTOCHROME_P450; 1.
PE   1: Evidence at protein level;
KW   Glycoprotein; Heme; Iron; Membrane; Metal-binding; Monooxygenase;
KW   Oxidoreductase; Reference proteome; Transmembrane; Transmembrane helix.
FT   CHAIN           1..530
FT                   /note="Cytochrome P450 monooxygenase apf7"
FT                   /id="PRO_0000437162"
FT   TRANSMEM        6..26
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   METAL           464
FT                   /note="Iron (heme axial ligand)"
FT                   /evidence="ECO:0000250|UniProtKB:P04798"
FT   CARBOHYD        85
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ   SEQUENCE   530 AA;  60226 MW;  828B9E37B7A7A007 CRC64;
     MILFSVSPVS IWVFVIYAVT IIIAIYRLFF HPYAKYPGPF LAKLTSWYSI YHTYYGDLHI
     DIWECHNKYE LGNYVRYGPN RILVNTSEGL NAIYSQGKNT QKAKAYRKVS LVPGVHPTFS
     MIDNQGHAKL RRLVGQGLSN AHIRMYDQEL RQSALLFASR LGEEIDRFEP NQPHGNHDGW
     TSPKNVASWS NYFTFDVMSH LVYGTSYDLL TDSENHWVIE GVLGQMRRIS FLTMLPELED
     MRFDRILFPD ARRKAYRFSA KSREILEARK SKSEEMRHQD AKVDVFLRLL SAKDPETGES
     LSDKQLWAES NLLIIAGSDT SSTGLAASFF YLSRNPSAYD RVKQEVRSAL TTSEDISQGP
     KLLSCTYLRA CVLESLRLSP PLGGAMWRQT MPGGLFIAGS DHDFHIPGGC EVGTGVYAIH
     HNEEYYPEPF RFRPERWLPQ EVGDEAVAKA QSAFQAFSLG PRSCPGKNLA MLEIPFALAA
     VMMDYDFRKV DSPLGGVGEG KGKFVGQYQT FWAFTSIKDG PYIQFKRREP
//