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   07-JUN-2017, entry version 18.
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)
OS   (Bakanae and foot rot disease fungus) (Fusarium fujikuroi).
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina;
OC   Sordariomycetes; Hypocreomycetidae; Hypocreales; Nectriaceae;
OC   Fusarium; 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.,
RA   Bald T., Wingfield B.D., Ophir R., Freeman S., Hippler M., Smith K.M.,
RA   Brown D.W., Proctor R.H., Muensterkoetter M., Freitag M., Humpf H.-U.,
RA   Gueldener U., Tudzynski B.;
RT   "Deciphering the cryptic genome: genome-wide analyses of the rice
RT   pathogen Fusarium fujikuroi reveal complex regulation of secondary
RT   metabolism and 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
RT   secondary metabolite gene cluster in the rice pathogen Fusarium
RT   fujikuroi.";
RL   PLoS ONE 9:E103336-E103336(2014).
CC   -!- FUNCTION: Cytochrome P450 monooxygenase; part of the gene cluster
CC       that mediates the biosynthesis of the cyclic tetrapeptide apicidin
CC       F (APF) (PubMed:25058475). The non-ribosomal peptide synthetase
CC       apf1 incorporates four different amino acids to produce apicidin
CC       F: L-phenylalanine, D-pipecolic acid (D-pip), N-methoxy-L-
CC       tryptophan and L-2-aminooctanedioic acid (PubMed:25058475). L-
CC       Phenylalanine is the only proteinogenic amino acid directly used
CC       by apf1 (PubMed:24195442, PubMed:25058475). The 3 other apf1
CC       substrates are non-proteinogenic and have to be modified by other
CC       enzymes of the cluster (PubMed:25058475). Lysine is converted to
CC       delta-1-pyrroline-5-carboxylate (P5C) which is reduced to L-
CC       pipecolic acid (L-pip) by apf3 (PubMed:25058475). L-pip is
CC       epimerized to D-pip, probably by apf1 activity, prior to
CC       incorporation (PubMed:25058475). L-Tryptophan is N-oxidyzed by one
CC       of the cytochrome P450 monooxygenases (apf7 or apf8), and further
CC       methylated at the hydroxy group by the O-methyltransferase apf6 to
CC       yield N-methoxy-L-tryptophan (PubMed:25058475). The synthesis of
CC       the fourth apf1 substrate is more complex (PubMed:25058475). The
CC       fatty acid synthase apf5 is involved in the synthesis of the
CC       octanoic acid backbone of L-2-aminooctanedioic acid by fixing one
CC       acetyl-CoA unit and three malonyl-CoA units (PubMed:25058475).
CC       Then one of the cytochrome P450 monooxygenases (apf7 or apf8) may
CC       oxidize this backbone to 2-oxooctanoic acid (PubMed:25058475). The
CC       aminotransferase apf4 is predicted to catalyze the exchange of the
CC       keto group with an amino group (PubMed:25058475). The next step
CC       would be the oxidation of 2-aminooctanoic acid by one of the
CC       cytochrome P450 monooxygenases (apf7 or apf8). The last step is
CC       the oxidation of 2-amino-8-hydroxyoctanoic acid to 2-
CC       aminooctanedioic acid is catalyzed by the FAD-dependent
CC       monooxygenase apf9 (PubMed:25058475).
CC       {ECO:0000269|PubMed:24195442, 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
CC       eight-base-pair motif 5'-TGACGTGA-3' called the 'Api-box' that is
CC       found in all promoters of the apicidin F cluster except in the
CC       promoter region of apf2 itself (PubMed:25058475).
CC       {ECO:0000269|PubMed:25058475}.
CC   -!- BIOTECHNOLOGY: Apicidin F, like the other known apicidins, is a
CC       cyclic tetrapeptides with anti-malarial properties via histone
CC       deacetylase inhibitory activity (PubMed:24195442).
CC       {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   EnsemblFungi; EBT00022337869; EBP00022352889; EBG00022322873.
DR   OrthoDB; EOG092C1JS2; -.
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   InterPro; IPR001128; Cyt_P450.
DR   InterPro; IPR017972; Cyt_P450_CS.
DR   InterPro; IPR002401; Cyt_P450_E_grp-I.
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   Complete proteome; Glycoprotein; Heme; Iron; Membrane; Metal-binding;
KW   Monooxygenase; Oxidoreductase; Reference proteome; Transmembrane;
KW   Transmembrane helix.
FT   CHAIN         1    530       Cytochrome P450 monooxygenase apf7.
FT                                /FTId=PRO_0000437162.
FT   TRANSMEM      6     26       Helical. {ECO:0000255}.
FT   METAL       464    464       Iron (heme axial ligand).
FT                                {ECO:0000250|UniProtKB:P04798}.
FT   CARBOHYD     85     85       N-linked (GlcNAc...) asparagine.
FT                                {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
//