APF12_GIBF5
ID APF12_GIBF5 Reviewed; 961 AA.
AC S0DLN7;
DT 07-SEP-2016, integrated into UniProtKB/Swiss-Prot.
DT 18-SEP-2013, sequence version 1.
DT 03-AUG-2022, entry version 32.
DE RecName: Full=Cytochrome b5-like reductase apf12 {ECO:0000303|PubMed:25058475};
DE EC=1.-.-.- {ECO:0000305|PubMed:25058475};
DE AltName: Full=Apicidin F synthesis protein 12 {ECO:0000303|PubMed:25058475};
GN Name=apf12 {ECO:0000303|PubMed:25058475}; ORFNames=FFUJ_00009;
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 b5-like reductase; 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:23825955,
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=FAD; Xref=ChEBI:CHEBI:57692; Evidence={ECO:0000305};
CC -!- PATHWAY: Secondary metabolite biosynthesis.
CC {ECO:0000269|PubMed:25058475}.
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 flavoprotein pyridine nucleotide cytochrome
CC reductase family. {ECO:0000305}.
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DR EMBL; HF679023; CCT63355.1; -; Genomic_DNA.
DR AlphaFoldDB; S0DLN7; -.
DR SMR; S0DLN7; -.
DR STRING; 5127.CCT63355; -.
DR PRIDE; S0DLN7; -.
DR EnsemblFungi; CCT63355; CCT63355; FFUJ_00009.
DR VEuPathDB; FungiDB:FFUJ_00009; -.
DR HOGENOM; CLU_308347_0_0_1; -.
DR Proteomes; UP000016800; Chromosome 1.
DR GO; GO:0020037; F:heme binding; IEA:InterPro.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0016491; F:oxidoreductase activity; IEA:UniProtKB-KW.
DR GO; GO:0019441; P:tryptophan catabolic process to kynurenine; IEA:InterPro.
DR Gene3D; 3.10.120.10; -; 1.
DR Gene3D; 3.40.50.80; -; 1.
DR InterPro; IPR001199; Cyt_B5-like_heme/steroid-bd.
DR InterPro; IPR036400; Cyt_B5-like_heme/steroid_sf.
DR InterPro; IPR017927; FAD-bd_FR_type.
DR InterPro; IPR039261; FNR_nucleotide-bd.
DR InterPro; IPR017938; Riboflavin_synthase-like_b-brl.
DR InterPro; IPR037217; Trp/Indoleamine_2_3_dOase-like.
DR Pfam; PF00173; Cyt-b5; 1.
DR SMART; SM01117; Cyt-b5; 1.
DR SUPFAM; SSF140959; SSF140959; 1.
DR SUPFAM; SSF52343; SSF52343; 1.
DR SUPFAM; SSF55856; SSF55856; 1.
DR SUPFAM; SSF63380; SSF63380; 1.
DR PROSITE; PS50255; CYTOCHROME_B5_2; 1.
DR PROSITE; PS51384; FAD_FR; 1.
PE 1: Evidence at protein level;
KW FAD; Flavoprotein; Heme; Iron; Metal-binding; NAD; NADP; Oxidoreductase;
KW Reference proteome.
FT CHAIN 1..961
FT /note="Cytochrome b5-like reductase apf12"
FT /id="PRO_0000437165"
FT DOMAIN 429..548
FT /note="FAD-binding FR-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00716"
FT DOMAIN 716..793
FT /note="Cytochrome b5 heme-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00279"
FT BINDING 298
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:P08165"
FT BINDING 453..456
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:P08165"
FT BINDING 499..500
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:P08165"
FT BINDING 753..755
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:P08165"
FT BINDING 753
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:P08165"
SQ SEQUENCE 961 AA; 106319 MW; 5D4715BE1801B1E9 CRC64;
MGIAQPGELA PVPRFRHLPF TIPNGIGRDT YLKIHNVMNH LGRAVLVGQH RRLIQALSSD
LGVDSLVAMV SISMQDSEVC SAFSVYLTTL EQAYHWPRES TLSTPEQLED HKLVIQMLQQ
PELRDTLVAS VHAQYDHSAT PAQVALSALS IAKQMIDQAT ETRSNKTKLP TEIQDLVNLL
YRTSRGDWFI QGNYTDPDSH KEFGRLHEVI RTNGTQRSVQ EIFQRFNGIS WLQRMPLLHQ
NFASNSSILC AAYADLQVAM ALARDELFSM VIDEPIWGLT FAKFSKGVGL CTIGAGGADC
PMFRMMDALC GRADNINQAA LLDELDFRSR FFPPGMRALI NDLVTAPSVR SHISSGEASY
ELTQAFRAME QIRYDLYEMH RKKAMRIALA LRAGQQATSS GVQNATTPEK YIASTLSAAI
KVRFGQEPAR PQVDAFAWST PLLCSDTGVI QTSRIQFVFS TPLAVSPGDS LRVAVEVEQG
DWHIRTYSIT HAYARQGSSK ARDQICQAVG SAEICVRSKG QVSSFLCNQK TGFPVRVMIK
PAPHFRIAGN TSPHEETLFV AQGGAVCVFL AWLAWQKQLV GTYRLVVGAR NYNMLAYVGQ
LEKISSSFGS HLIVHVVLSR PGHGDIQRFV PGNIKASTGR VTHHLGLFSS CSTKATYVCG
SASFALDVVR CLSQGPGTKR EVPKVSRLQP IVTSRLPHFR LHVAAATENG TDKPCLNQIT
KLELALHNSP GDLWIALGDR VFDISQVPSF HPGGEKVLMY RAGRQAQDVF DTVHEGCYMI
SSLLNEMVIG RLDSARGEFS QWEDYLDKIV EIQNDLTNHS RIEQAPTGSI EQLAESPPVE
ILRGATNCFV KGWSSLLQQS GIGDSGVVSL LSSHQDAISA LDAHVRMVYE NDFEDPVRYA
NALRKIFDAH SRLVCGIHTA IDELKRHIVE RLVEGDEPEL TSLHISTARI SQQLRETSKS
Y
