APF7_GIBF5
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 03-AUG-2022, entry version 28.
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 AlphaFoldDB; S0DPM1; -.
DR SMR; S0DPM1; -.
DR STRING; 5127.CCT63357; -.
DR PRIDE; S0DPM1; -.
DR EnsemblFungi; CCT63357; CCT63357; FFUJ_00007.
DR VEuPathDB; FungiDB: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 BINDING 464
FT /ligand="heme"
FT /ligand_id="ChEBI:CHEBI:30413"
FT /ligand_part="Fe"
FT /ligand_part_id="ChEBI:CHEBI:18248"
FT /note="axial binding residue"
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
