APF9_GIBF5
ID APF9_GIBF5 Reviewed; 585 AA.
AC S0DL65;
DT 07-SEP-2016, integrated into UniProtKB/Swiss-Prot.
DT 18-SEP-2013, sequence version 1.
DT 03-AUG-2022, entry version 31.
DE RecName: Full=FAD-linked oxidoreductase apf9 {ECO:0000303|PubMed:25058475};
DE EC=1.-.-.- {ECO:0000305|PubMed:25058475};
DE AltName: Full=Apicidin F synthesis protein 9 {ECO:0000303|PubMed:25058475};
DE Flags: Precursor;
GN Name=apf9 {ECO:0000303|PubMed:25058475}; ORFNames=FFUJ_00005;
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, INDUCTION, AND DISRUPTION PHENOTYPE.
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: FAD-linked oxidoreductase; 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=FAD; Xref=ChEBI:CHEBI:57692;
CC Evidence={ECO:0000250|UniProtKB:P08159};
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 -!- DISRUPTION PHENOTYPE: Leads to the loss of apicidin F production but
CC accumulates apicidin K (PubMed:25058475).
CC {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 oxygen-dependent FAD-linked oxidoreductase
CC family. {ECO:0000305}.
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DR EMBL; HF679023; CCT63359.1; -; Genomic_DNA.
DR AlphaFoldDB; S0DL65; -.
DR SMR; S0DL65; -.
DR STRING; 1279085.S0DL65; -.
DR EnsemblFungi; CCT63359; CCT63359; FFUJ_00005.
DR VEuPathDB; FungiDB:FFUJ_00005; -.
DR HOGENOM; CLU_018354_4_4_1; -.
DR BioCyc; MetaCyc:MON-19330; -.
DR Proteomes; UP000016800; Chromosome 1.
DR GO; GO:0071949; F:FAD binding; IEA:InterPro.
DR GO; GO:0016491; F:oxidoreductase activity; IEA:UniProtKB-KW.
DR Gene3D; 3.30.465.10; -; 2.
DR InterPro; IPR012951; BBE.
DR InterPro; IPR016166; FAD-bd_PCMH.
DR InterPro; IPR036318; FAD-bd_PCMH-like_sf.
DR InterPro; IPR016169; FAD-bd_PCMH_sub2.
DR InterPro; IPR006094; Oxid_FAD_bind_N.
DR InterPro; IPR006093; Oxy_OxRdtase_FAD_BS.
DR Pfam; PF08031; BBE; 1.
DR Pfam; PF01565; FAD_binding_4; 1.
DR SUPFAM; SSF56176; SSF56176; 1.
DR PROSITE; PS51387; FAD_PCMH; 1.
DR PROSITE; PS00862; OX2_COVAL_FAD; 1.
PE 1: Evidence at protein level;
KW FAD; Flavoprotein; Glycoprotein; Oxidoreductase; Reference proteome;
KW Signal.
FT SIGNAL 1..19
FT /evidence="ECO:0000255"
FT CHAIN 20..585
FT /note="FAD-linked oxidoreductase apf9"
FT /evidence="ECO:0000255"
FT /id="PRO_5004485041"
FT DOMAIN 108..294
FT /note="FAD-binding PCMH-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00718"
FT MOD_RES 145
FT /note="Pros-8alpha-FAD histidine"
FT /evidence="ECO:0000250|UniProtKB:P08159"
FT CARBOHYD 40
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 92
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 117
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 352
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 412
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 495
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ SEQUENCE 585 AA; 63587 MW; 3B7147B41676255E CRC64;
MKPHTVSLVL SNLASLAAAT CKCTPGHACW PSLEEWSRFN SSIGGQLIQS SPVAEACYSG
PKDNAACQNI EKSWTDDVFQ VSQPIGYAWP LNLSCPLPTP GLDTKCSIGN SPVYVVNVTC
EEDITRGIKF AQEKNLRLVV KSTGHDSQQR STGYGSLSIW LHNFRKGFRF QGHNPVLATC
PKSGWKGSTL TINGGYSWRD IYPAAQKQGL IVIGGLDRGP CSTGGWTQGG GHSPGTHYFG
IGADQVLSAR VVLASGKIVV ASPCENEDLF FAIRGGGGGT FGVVTEITVK TYPTKALSTI
NLIVGSKGDE TVPKFLDAVA TIYSLLPGLS KKGFAGYGNW VVRALSPITA KNYTNLYGQS
WTLLGATQQE AENLFQPFKE EIVKHQSENG LEVTVSSGTF RDYFSYYYSM GNGTDSAVGG
VSALASRLLD TEALQGNRKD LRKFLDSITQ GSAVYHTLIH HGLEAAADVK ADPTSAVLPG
WYKSILLDEF EIPMNTTDVD AYAGSFEYLR NELVPLYESL SPDTGTYMNE ADWGNMNWKK
DFFGSHWDRL LKVKTRYDPE GFFYCPKCVG SDDWVENKGG SLCRA
