APF5_GIBF5
ID APF5_GIBF5 Reviewed; 1606 AA.
AC S0DL59;
DT 07-SEP-2016, integrated into UniProtKB/Swiss-Prot.
DT 18-SEP-2013, sequence version 1.
DT 25-MAY-2022, entry version 45.
DE RecName: Full=Fatty acid synthase apf5 {ECO:0000303|PubMed:25058475};
DE EC=2.3.1.41 {ECO:0000255|PROSITE-ProRule:PRU10022, ECO:0000305|PubMed:25058475};
DE AltName: Full=Apicidin F synthesis protein 5 {ECO:0000303|PubMed:25058475};
GN Name=apf5 {ECO:0000303|PubMed:25058475}; ORFNames=FFUJ_00010;
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: Fatty acid synthase; part of the gene cluster that mediates
CC 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 -!- CATALYTIC ACTIVITY:
CC Reaction=a fatty acyl-[ACP] + H(+) + malonyl-[ACP] = a 3-oxoacyl-[ACP]
CC + CO2 + holo-[ACP]; Xref=Rhea:RHEA:22836, Rhea:RHEA-COMP:9623,
CC Rhea:RHEA-COMP:9685, Rhea:RHEA-COMP:9916, Rhea:RHEA-COMP:14125,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:16526, ChEBI:CHEBI:64479,
CC ChEBI:CHEBI:78449, ChEBI:CHEBI:78776, ChEBI:CHEBI:138651;
CC EC=2.3.1.41; Evidence={ECO:0000255|PROSITE-ProRule:PRU10022,
CC ECO:0000305|PubMed:25058475};
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 thiolase-like superfamily. Fungal fatty acid
CC synthetase subunit alpha family. {ECO:0000305}.
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DR EMBL; HF679023; CCT63354.1; -; Genomic_DNA.
DR AlphaFoldDB; S0DL59; -.
DR SMR; S0DL59; -.
DR STRING; 1279085.S0DL59; -.
DR EnsemblFungi; CCT63354; CCT63354; FFUJ_00010.
DR VEuPathDB; FungiDB:FFUJ_00010; -.
DR HOGENOM; CLU_000114_0_0_1; -.
DR Proteomes; UP000016800; Chromosome 1.
DR GO; GO:0005835; C:fatty acid synthase complex; IEA:InterPro.
DR GO; GO:0004316; F:3-oxoacyl-[acyl-carrier-protein] reductase (NADPH) activity; IEA:InterPro.
DR GO; GO:0004315; F:3-oxoacyl-[acyl-carrier-protein] synthase activity; IEA:UniProtKB-EC.
DR GO; GO:0008897; F:holo-[acyl-carrier-protein] synthase activity; IEA:InterPro.
DR GO; GO:0042759; P:long-chain fatty acid biosynthetic process; IEA:InterPro.
DR Gene3D; 3.40.47.10; -; 1.
DR InterPro; IPR016035; Acyl_Trfase/lysoPLipase.
DR InterPro; IPR040899; Fas_alpha_ACP.
DR InterPro; IPR026025; FAS_alpha_yeast.
DR InterPro; IPR041550; FASI_helical.
DR InterPro; IPR018201; Ketoacyl_synth_AS.
DR InterPro; IPR014031; Ketoacyl_synth_C.
DR InterPro; IPR014030; Ketoacyl_synth_N.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR InterPro; IPR009081; PP-bd_ACP.
DR InterPro; IPR016039; Thiolase-like.
DR Pfam; PF18325; Fas_alpha_ACP; 1.
DR Pfam; PF18314; FAS_I_H; 1.
DR Pfam; PF00109; ketoacyl-synt; 1.
DR Pfam; PF02801; Ketoacyl-synt_C; 1.
DR PIRSF; PIRSF000454; FAS_yeast_alpha; 1.
DR SUPFAM; SSF51735; SSF51735; 1.
DR SUPFAM; SSF52151; SSF52151; 1.
DR SUPFAM; SSF53901; SSF53901; 2.
DR PROSITE; PS00606; B_KETOACYL_SYNTHASE; 1.
DR PROSITE; PS50075; CARRIER; 1.
PE 1: Evidence at protein level;
KW Phosphopantetheine; Phosphoprotein; Reference proteome; Transferase.
FT CHAIN 1..1606
FT /note="Fatty acid synthase apf5"
FT /id="PRO_0000437160"
FT DOMAIN 142..218
FT /note="Carrier"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT ACT_SITE 1182
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10022"
FT MOD_RES 177
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
SQ SEQUENCE 1606 AA; 175724 MW; 9B979110B4A66562 CRC64;
MHPDVEQELA YTLLIELMAH QFAYPVRWIE TQDHILGEVN AERIIEIGPS PILTNMMKRT
IASRFSNSDQ ALNINRHLMS PDNGNPDIYY KYEPTEEPDL PELGSQSNTV KVSGSPAWEV
QRPVTASHIP SGPVDEIEDT KVPVSAILIS LLAPKLKKDP RAIPMTGTIS NLVGGRSTLS
NEIVGDLLAE FPNRVPDKPE EMPLSSLSET LSTSHDGQLG KATSALVMKM VSSRLPGGYS
LSNARLYLRE KWGLPPRRQD AVFLLALQRQ PTSRLLSSTD VDSFLDANAA AYFGQENLSI
PSRGSVQSAA PAVDAKALLL AKQQNDALLR DIMGVIQGHT AAKNESQDAT LQASDSEAAA
TKKLDMWISE HGDDYAKGMA PIFDAKKQRI YDSYWNWNAQ DTILLFQRKL QGQMSSVKEL
EQLSTSIVNR ACGRTLEQLD YIIAQAERDP TVDSGLLKPM QLLRQTCVET QERQPVFINL
SPDMAPLTTI SSDGRLIFSE IPRALPCSKI LSTNEASSIA FPVSRADGVA VSYSPQLTEI
LCHDLKDSRR SGFSFSGKNV LLTGAGEGSI GNHILRHLLA GGARVTVTTS SFSEKVTAMF
QSIYARHGSK GSVLRVVPFN QGSHGDVQNL VKYIYADASW DLDFILPFAA ISENGRDIED
LDSKSEIAHR AMLTNLVRLV GAVASQKRQR DTITRPATVV LPLSPNHGLL GNDGLYSESK
RSLETLIPKW SSETWGSYIA LAGVIIGWTR GTGLMDSNDV IAQAVESLGV RTFSAVEMAA
NIVSVMGGRF NAECQETPII VDMGGGLGSV KNFKAKLTSA RQELNAYAEL KRLTAQESSR
DKAYVATDAH AKTSKRLRGR ANILLPLPKN LNYEVDIAPF AASLDGMVDL SRVVVITGFA
ELGPLGNSRT RWEMEESGTL SLEGCVEMAW LMGLITYHNG IDKKGDHYSG WVDTKTSDAI
CDDEIPGKYL EFMAKHSGIR EVEPEISDNG YDPSKKESLI EVALQRDLAP FETSIETAET
LKRQHGDKAI VTQDASSGNC QVQLKAGAVV MVPRASRFNR TVAGQIPLGW TAKRYGISDD
IIEQVDPVTL FSLVCTVEAL LCSGIIDPYE FYQHIHVSQF ANCLGSSMGG LTSLRKMHRD
RYLDRSVKSD LVQETFINTT GAWINMLLSS SSGPIRTPVG ACASSLESLD TACDLIMLKK
AKVCLVGGFE DFVEDLSYEF GCMKATCDTD AEYAAGRVPK EMSRPTASSR SGFVESQGCG
VQVLTSAELA LEMGLPIFGI VAYTSMAADK AGRSVPAPGK GVLTNAREKS TIPNPMLSLG
YRKRLLELRR TQIYQNISDH LDILNSEIAL FQESETASPG DLKAFRENRE LRIRQDAQAQ
DAEVTFSLGN QFWKSQDAGD ISPIRGSLAV WGLGIDDISV ASLHGTSTVQ NDLNETMVIQ
EQMKHLGRRQ GNLLPCVCQK WLTGHSKGAA GAWMVNGCLQ MMNTGLVPGN RNADNVDEKL
REHRHLAFPN TNLQMDDIKA CSVTSFGFGQ KGGQALLVHP RYLFATIGRE RYDGYISKRD
KRWRKACFRL SEAMVQGNMV SKCIKTEAPY TSADGVAALL DPTARF
