APF1_GIBF5
ID APF1_GIBF5 Reviewed; 5084 AA.
AC S0DLP2;
DT 07-SEP-2016, integrated into UniProtKB/Swiss-Prot.
DT 18-SEP-2013, sequence version 1.
DT 03-AUG-2022, entry version 37.
DE RecName: Full=Apicidin F synthase {ECO:0000305};
DE EC=6.3.2.- {ECO:0000305|PubMed:25058475};
DE AltName: Full=Apicidin F synthesis protein 1 {ECO:0000303|PubMed:25058475};
DE AltName: Full=Non-ribosomal peptide synthetase apf1 {ECO:0000303|PubMed:25058475};
DE Short=NRPS apf1 {ECO:0000303|PubMed:25058475};
GN Name=apf1 {ECO:0000303|PubMed:25058475}; ORFNames=FFUJ_00003;
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: Non-ribosomal peptide synthetase; part of the gene cluster
CC that mediates the biosynthesis of the cyclic tetrapeptide apicidin F
CC (APF) (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 -!- 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
CC (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 NRP synthetase family. {ECO:0000305}.
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DR EMBL; HF679023; CCT63360.1; -; Genomic_DNA.
DR SMR; S0DLP2; -.
DR STRING; 1279085.S0DLP2; -.
DR PRIDE; S0DLP2; -.
DR EnsemblFungi; CCT63360; CCT63360; FFUJ_00003.
DR VEuPathDB; FungiDB:FFUJ_00003; -.
DR HOGENOM; CLU_000022_60_0_1; -.
DR BioCyc; MetaCyc:MON-19327; -.
DR Proteomes; UP000016800; Chromosome 1.
DR GO; GO:0016853; F:isomerase activity; IEA:UniProtKB-KW.
DR GO; GO:0016874; F:ligase activity; IEA:UniProtKB-KW.
DR GO; GO:0031177; F:phosphopantetheine binding; IEA:InterPro.
DR Gene3D; 1.10.1200.10; -; 4.
DR Gene3D; 3.30.300.30; -; 4.
DR Gene3D; 3.30.559.10; -; 5.
DR Gene3D; 3.40.50.12780; -; 4.
DR InterPro; IPR010071; AA_adenyl_domain.
DR InterPro; IPR036736; ACP-like_sf.
DR InterPro; IPR045851; AMP-bd_C_sf.
DR InterPro; IPR020845; AMP-binding_CS.
DR InterPro; IPR000873; AMP-dep_Synth/Lig.
DR InterPro; IPR042099; ANL_N_sf.
DR InterPro; IPR023213; CAT-like_dom_sf.
DR InterPro; IPR001242; Condensatn.
DR InterPro; IPR020806; PKS_PP-bd.
DR InterPro; IPR009081; PP-bd_ACP.
DR InterPro; IPR006162; Ppantetheine_attach_site.
DR Pfam; PF00501; AMP-binding; 4.
DR Pfam; PF00668; Condensation; 5.
DR Pfam; PF00550; PP-binding; 3.
DR SMART; SM00823; PKS_PP; 2.
DR SUPFAM; SSF47336; SSF47336; 4.
DR TIGRFAMs; TIGR01733; AA-adenyl-dom; 4.
DR PROSITE; PS00455; AMP_BINDING; 3.
DR PROSITE; PS50075; CARRIER; 4.
DR PROSITE; PS00012; PHOSPHOPANTETHEINE; 1.
PE 1: Evidence at protein level;
KW Isomerase; Ligase; Phosphopantetheine; Phosphoprotein; Reference proteome;
KW Repeat.
FT CHAIN 1..5084
FT /note="Apicidin F synthase"
FT /id="PRO_0000437156"
FT DOMAIN 731..808
FT /note="Carrier 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT DOMAIN 2341..2415
FT /note="Carrier 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT DOMAIN 3463..3539
FT /note="Carrier 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT DOMAIN 4554..4631
FT /note="Carrier 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT REGION 209..606
FT /note="Adenylation 1"
FT /evidence="ECO:0000255"
FT REGION 822..1124
FT /note="Condensation 1"
FT /evidence="ECO:0000255"
FT REGION 1309..1609
FT /note="Condensation 2"
FT /evidence="ECO:0000255"
FT REGION 1788..2192
FT /note="Adenylation 2"
FT /evidence="ECO:0000255"
FT REGION 2415..2441
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2478..2755
FT /note="Condensation 3"
FT /evidence="ECO:0000255"
FT REGION 2935..3328
FT /note="Adenylation 3"
FT /evidence="ECO:0000255"
FT REGION 3581..3866
FT /note="Condensation 4"
FT /evidence="ECO:0000255"
FT REGION 4029..4426
FT /note="Adenylation 4"
FT /evidence="ECO:0000255"
FT REGION 4669..4948
FT /note="Condensation 5"
FT /evidence="ECO:0000255"
FT COMPBIAS 2416..2441
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 768
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT MOD_RES 2376
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT MOD_RES 3500
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT MOD_RES 4592
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
SQ SEQUENCE 5084 AA; 562186 MW; DBCE0E79CE257757 CRC64;
MAIKMIDKQV LACNLDAFAG RVTNSTDINE QAIEWLSPTP SAVTLEAAWC VTLRLYTGLD
HLSFGSLTQD GIVATKLCNL GPHDTLEDVC SHVQLYDYSD DTVCHYNTAV IFKLDENEGK
KLSELIPRGI DVALMVTGSN LGVLARASFM DADEARNLCQ NFRHVLNCFQ EPNQAVRGIT
LSDNDVNQIL SWNKSQLTRT ESLIHDQFAR ILQRQPDKSA IESWDGNMTY RELDAASSSL
AESLSRANIG PGSWVLFCFN KSRWAIVSML AILKAGGACV PLDPRHPKSR VVQILQATGA
QHILVGDADN DIKNRLCNEF PSVKVIGVPH HEVCESQDID TISLSFDSPA IGLFTSGSTG
TPKGIVATHA TICTGASSYA HHIGADDKTR VLQFASYTFD VCMVDVFTAL LHGGTLCIPS
EEERMTGLQE YISRTQPNWA ALTPTVARVL DPALSSKSIR KILLVGEMVR ESDIAEWLDS
GVQVYNVYGP AENNLITTAA KAIRGRASNV GTGINTHTWV ADVENERLVP IGAVGELICS
GPHLTPGYLN DPERTASSFF EDLSWIPNMM DNKPFSRRFY RSGDLVRYCA DGSLQCVGRL
DSQVKLGGQR VELSEIESYI KSHNAAVLVP KAGSMKNKLI AVLEGAGSSG QSLGISSCDP
GVAQQVEQVL RKNLPSYMCP SIWISVPHLP LSSSGKLDRK VLMNKLETLS HEEYLGLILD
HAQDEDDQDG HETDNCQRLL REACSQVLNI PVERIAMSRA FAGHGGDSIT AMQVSSLIKR
TQTLVVTVKD LLTCHSLAEA ASSMREVVTS IQVPTAHPGK LYPLSPIQRL FMATAPTSVT
WNHYNQSVLL RIRERRSSDH VKESLGGVVR RHAMLRGRFQ RVSSSEWMQR ILPDDQGNLF
FEYFPDASDY KQREALMLKA RESLDIESGP LLRAQLFDGQ VEQGMLLFIV SHHLVVDLVS
WRVILEELEV SLAQPYGNTT DANDISALLL PQESVPFPVW SELQHEAAKN MDPDRVIPQQ
YAVPAPDFSY WGISSARNVY RDVIEKSISL GDMTTKNVLY ECHEALQTEP VDIFLSAILL
SFKRAFPERP IPPIFNEGHG REPWTSDLDI SRTVGWFTTM FPIYVPNISA GDVVDTVRRV
KDFRKGCAEN GFQYFSTKYL HEQGRKTFKD HIPAEIMFNY EGRYQSLEKE KSLLMAEAWE
AGEALSDSAP ELQRFCLFEL SAAVLTDGEI HFTMAWNSRA RYQERISLWL TRLLPAVIDE
IVTYLMLEKR QYTLSDLSQA RLSDYSDLET LMASVSTIPG IDSIEGVEEI YCGSPMQDSL
ALSQSRISGG VYEIDLTWEV TDGRQGNYQV DVNRLVLAWN DVVARHAALR TVFLEAASSS
NDVMLHQVVL RKYRPSTILM HTRDSSQALK QLSSCASYKK RGILIDKRPP HALAICSTDE
GRTFVRFQVN HILFDGTSIA PLLRDLSRAY RNSHEVRREW TWNPFANFIR YIRDEKRRSD
DLAYWKSYLA TARPCQFPTL KHEESIEAPG TEQQRGAVQV CMSDKPSSLR NFLADMGVTV
PTLVQLVWAL VLRMYTSDSQ VAFGYLASGR DAPVVDIEQA VGPFISILVH FLDFDNEGQL
PIADMLQRIQ DRSARSISHQ SRSLAEIQDA IGLTGSSLLF NTGISFMPKW TKDMQLRNGS
GLIFDQIAAN DPTEFDISLI VETGDDGVDG MCIYVDYRTS TVGRMHAINI AASFDHILSQ
IIQDPSVPLN DVSGISTRDF DQISNWNRLL SPPKDKCLHD LFIEKVIEDP TREAVFSWDG
SMSYGELHDL SARLANYLVH LGVGPEQMIP ICFEKSVWTV VTILAVLKAG GCFVLLDPTH
PASRLWNIVG EIEASILLCS PLTNRSKKLD ASPDMNARKA AIIEIHPSFV NNLKSVSRES
QHTPLCPSLS PDNAAYVVFT SGSTGIPKGV VVTHRAVVTG LDELGRAAGM TAMGSGTRTL
QFASYSFDAS IADIFCALQL GGCVCVMSDE GRSPADITDF IQRSRATYAG ITPSFASLLD
PRLVPSLRVL CFSGEALPAS QIEAWSGYVK MVNMYGPTEA SIACIANSEV TRTTDASNIG
RAFRGSTWIV DENDHNQLRA IGSSGELLIE GPILAREYLK RPEQTAQAFI SNPPWLQNIR
PNSRLYKTGD MVRYNTNGTI SYIGRKDNQI KINGQRVEVS EIEETLRASI EPEAGLITVE
LLDRKALGEA DVLTAFVYIA GHDPSSTRDD KADNKKPFTI PDNPLLLEYF RSMLPRLESS
SSKMPRYMVP QAYIPIDSLP LTTSGKVDRR ALRHAAAQLN RNQLFSFASS LDMVHEPSVD
VVKDDPVSEL AHLWESVLNV RVSGTQSNFF RLGGNSMAAM NLRSQARKAG FQLSVADILA
NPTLSDMAKG MAPLSLTAPE STSSSSPQSF STSTSTTIIE NDPDTSPFSL LRTRGIALNE
GLWQQMFDNA DILWSEVEDI FPCTPMQEGL MVLSAHREGH GAYALHAPYK LPSDLDLAKL
QFAWEQTTMV HAILRSRIVT HSQGALIVLQ KSPVVVQQST CSTLDDHLEE QRRLIFGYGV
PLFRMTMVFD QIAQCHYFVM SIHHALFDGW SFSRMWDTAL AIYQGRQLSR DIPSFQSFVQ
HLGAAPLSAS KEYWKSHLVE QDRDGFQFPA VPSTHKPIAT ASASFEFAFQ STIAMSAGVT
PSTMVHAAWA ILLSQYTASS TVNFGVTLSG RDFPMPGLDQ VVGATIVTLP RQLNINLNQN
VIEFLEYVQQ EAANVIPHQY LGIHEIRALG LEAQQACNFS TLILVNHNTV DLDSPLSVFG
ITQVPVDSVD FHPYPLAVEF TVQPESLVVN VCYDPVCIGG SMVESVMQQY DHVLQSLSEG
LMCSSGLSGT NLASIMTGIA PAHLQKMLDW NKDGHRYGAS RQTHLVLDHI GLNTRNNPRA
RAVVADDSTL SYAELNRLAR VVSHRITQLD ISGEFIAVCF DKSAAAIVSM LAVLQTGFAF
MPISASQPPA RLENLLTAAN VQVVLTSPAH TDLLSGLSSH RRIVPVDLKD IDQHEQMQLN
RSGSAVDKSR AAYLLYTSGT TGQPKGVVVQ HGAWSKAIAS QIDFFGFTRD TKMLQFSNYT
FDASIFEIFI TLCSGGCLFV PSEHSRVNDL EGFIRTNELN TITLTPTVAR VIRPGQLPCV
RQCLFGGESL TQSDIFAWAQ QGRRVTNCYG PTEACVFSCG RDIRLDATDT KVTNIGRPVG
INAWIISSMS GSISPIGAPG ELCLEGQMLA RGYLNDPERT QLSFSNHLPN NIPGKKNSRT
YRTGDMVCHE ADGTLNFLGR RDGQIKLRGH RIDVGEIEHH IQHAMADDST YHSSTVQVYW
KDTRNKSDAE LAALLRMDIQ HKECVMGVPC SLLSMPGRAD ESPTASQLKF KLRRILPEHM
TPNTFIAVQH FPTTASGKLD RSFAQRCVEY FVPYTQKEVN KNETWSSSEA IVREWWCSIL
GVNTDLICRH DNFFGLGGNS IYAIRLVGLA RSNGHHLQYE DVFSSPVLAD MASRLSRPED
SRVQSETRQP PEPFQLISES DLKSVMDDIL PLYNINKDEV EDIYPCTPLQ ATLMAETARH
RGVYILAESI QVPSSQMTLF QDAWLLMFKS YEILRTRIVL SHDQSHGEWQ VVMKYQPLTW
TEFPDAKSFI EFVYNTHDYG KPLVHLAILG GNGGRIKDTD HSVKVGLCVH HAAYDGWSLS
NIWRTITKKL TSSSSYSVGP YTPFNTYIRH LTEQDPEKAK SYWKERFSGL SSASLIPRPQ
DPGHQSSATD TIQRNLDLPT LSDHLLGKTA IVAQAAWAIT ISHYTANSDT LCGTILSGRE
YAAASVPGVE TIVGPTIATV PSRTTINYDS CVLDLITAVQ KDNLNAVRFS HMGLEQISRL
NLDCRQACKF DNLFWVQPDL DETPANSIIR DIINVRGFSS SPMVLEIQLP AEGQKVVVNM
SFDRVAVSNQ QAELIVDTYI TIMDNLLHAP LDTRLRSIAA LSPAHISQIS RVSSSPVEAV
QACVHDLVRK QVELSPSHTA IDAWDGSMAY AALDALSTSL AEKLSGLGIG PESPVCILFE
KSKWAIVAML GVVKTGGCFV PLNPQSPIKR LQHLVESVDA SIILVSPQYE ELSISLSLHH
VKILVISQDT IPSPISALKP SRAFPSSVGP QNAAYILFTS GSTGLPKGVV IEHQALCSSL
TVLSSRVGLN SNSRVFQFNA YWFDVMLLDV FGTLISGGTI CAPSESDCMD DLAGSINKFN
ANTIAALSTS VSRLIEPSSI PCLNTLGLGG EPVLSSDRDR WAPHVRLFSM YGPTETCIVS
LMTDMTSTTP ASLLGHPVGC RVWIVNPLKN DELAPLGGIG ELFIEGPGLA RYYLVDEDKT
AAAFLSNQSW TIQDPSFQGS RRFYKTGDLV RINTDGTVSW IGRKDHSQVK IRGQRVELAE
IEETIRQHIP SALTVAVDIL IDGERRILAA VFGTNLMLPG LSDTEVEVYM EKLIKGLLPK
LNGSLPKHMV PTAFIPLPFL PFLSTGKLDR KALHRLALPL AVELTKRTST NRQALKTPKE
RLLSALWSEV LSTSKGEPAG PADNFFNAGG DSMMAMKLVA MARHRGLTLS VVDIFKNPIL
SDMADLLGPL RHEEEPSKED STHMLPIDTS SKLKDSLYEV LTVPPDRIEQ IYPCTAYQEM
FLSGTEVWPG AHVTQFIFSI DKGTDMHRLE KAMGRCTAEF PTLRTRIVRH GESGQLLQVV
LHKGHEAPWS IHLTDDLDSA LDQEKKDHWM HSGLSEPLHR LSLVMNNSGC THLIWSLNHA
AYDAWSFGMM LRSLGQDRAN STRHSRTCLP FNGLIRHISK LRDASSESRR FWRSYIADIG
SQVLLFRYPS IADPRQDRLA VHQVSFPKHG GRSSTSLITA AWIMLLARLS HRKDITIAYL
VTGRTLPLGG IDTCPGPLIS KLPLRIQLLD EPRGLVDVAD LVRIETVRVM PHEHTGLDAI
KDLASQDDDD IHPHAASLLG RFPLDLAIHP AGHTDVDAAR SIGITHIGQK VVVPPPGTFS
AECSIISEDN YIAVSLAVIW DNRAMDEDDV NRVVEIWKDI IVRG
