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   08-MAY-2019, entry version 30.
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)
OS   (Bakanae and foot rot disease fungus) (Fusarium fujikuroi).
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina;
OC   Sordariomycetes; Hypocreomycetidae; Hypocreales; Nectriaceae;
OC   Fusarium; 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.,
RA   Bald T., Wingfield B.D., Ophir R., Freeman S., Hippler M., Smith K.M.,
RA   Brown D.W., Proctor R.H., Muensterkoetter M., Freitag M., Humpf H.-U.,
RA   Gueldener U., Tudzynski B.;
RT   "Deciphering the cryptic genome: genome-wide analyses of the rice
RT   pathogen Fusarium fujikuroi reveal complex regulation of secondary
RT   metabolism and 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
RT   secondary metabolite gene cluster in the rice pathogen Fusarium
RT   fujikuroi.";
RL   PLoS ONE 9:E103336-E103336(2014).
CC   -!- FUNCTION: Non-ribosomal peptide synthetase; part of the gene
CC       cluster that mediates the biosynthesis of the cyclic tetrapeptide
CC       apicidin F (APF) (PubMed:25058475). The non-ribosomal peptide
CC       synthetase apf1 incorporates four different amino acids to produce
CC       apicidin F: L-phenylalanine, D-pipecolic acid (D-pip), N-methoxy-
CC       L-tryptophan and L-2-aminooctanedioic acid (PubMed:25058475). L-
CC       Phenylalanine is the only proteinogenic amino acid directly used
CC       by apf1 (PubMed:24195442, PubMed:25058475). The 3 other apf1
CC       substrates are non-proteinogenic and have to be modified by other
CC       enzymes of the cluster (PubMed:25058475). Lysine is converted to
CC       delta-1-pyrroline-5-carboxylate (P5C) which is reduced to L-
CC       pipecolic acid (L-pip) by apf3 (PubMed:25058475). L-pip is
CC       epimerized to D-pip, probably by apf1 activity, prior to
CC       incorporation (PubMed:25058475). L-Tryptophan is N-oxidyzed by one
CC       of the cytochrome P450 monooxygenases (apf7 or apf8), and further
CC       methylated at the hydroxy group by the O-methyltransferase apf6 to
CC       yield N-methoxy-L-tryptophan (PubMed:25058475). The synthesis of
CC       the fourth apf1 substrate is more complex (PubMed:25058475). The
CC       fatty acid synthase apf5 is involved in the synthesis of the
CC       octanoic acid backbone of L-2-aminooctanedioic acid by fixing one
CC       acetyl-CoA unit and three malonyl-CoA units (PubMed:25058475).
CC       Then one of the cytochrome P450 monooxygenases (apf7 or apf8) may
CC       oxidize this backbone to 2-oxooctanoic acid (PubMed:25058475). The
CC       aminotransferase apf4 is predicted to catalyze the exchange of the
CC       keto group with an amino group (PubMed:25058475). The next step
CC       would be the oxidation of 2-aminooctanoic acid by one of the
CC       cytochrome P450 monooxygenases (apf7 or apf8). The last step is
CC       the oxidation of 2-amino-8-hydroxyoctanoic acid to 2-
CC       aminooctanedioic acid is catalyzed by the FAD-dependent
CC       monooxygenase apf9 (PubMed:25058475).
CC       {ECO:0000269|PubMed:24195442, 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
CC       eight-base-pair motif 5'-TGACGTGA-3' called the 'Api-box' that is
CC       found in all promoters of the apicidin F cluster except in the
CC       promoter region of apf2 itself (PubMed:25058475).
CC       {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
CC       cyclic tetrapeptides with anti-malarial properties via histone
CC       deacetylase inhibitory activity (PubMed:24195442).
CC       {ECO:0000269|PubMed:24195442}.
CC   -!- SIMILARITY: Belongs to the NRP synthase family. {ECO:0000305}.
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DR   EMBL; HF679023; CCT63360.1; -; Genomic_DNA.
DR   SMR; S0DLP2; -.
DR   EnsemblFungi; CCT63360; CCT63360; FFUJ_00003.
DR   BioCyc; MetaCyc:MONOMER-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; 3.30.559.10; -; 5.
DR   Gene3D; 3.40.50.12780; -; 4.
DR   InterPro; IPR010071; AA_adenyl_domain.
DR   InterPro; IPR036736; ACP-like_sf.
DR   InterPro; IPR020845; AMP-binding_CS.
DR   InterPro; IPR000873; AMP-dep_Synth/Lig.
DR   InterPro; IPR042099; AMP-dep_Synthh-like_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   Complete proteome; Isomerase; Ligase; Phosphopantetheine;
KW   Phosphoprotein; Reference proteome; Repeat.
FT   CHAIN         1   5084       Apicidin F synthase.
FT                                /FTId=PRO_0000437156.
FT   DOMAIN      731    808       Carrier 1. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00258}.
FT   DOMAIN     2341   2415       Carrier 2. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00258}.
FT   DOMAIN     3463   3539       Carrier 3. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00258}.
FT   DOMAIN     4554   4631       Carrier 4. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00258}.
FT   REGION      209    606       Adenylation 1. {ECO:0000255}.
FT   REGION      822   1124       Condensation 1. {ECO:0000255}.
FT   REGION     1309   1609       Condensation 2. {ECO:0000255}.
FT   REGION     1788   2192       Adenylation 2. {ECO:0000255}.
FT   REGION     2478   2755       Condensation 3. {ECO:0000255}.
FT   REGION     2935   3328       Adenylation 3. {ECO:0000255}.
FT   REGION     3581   3866       Condensation 4. {ECO:0000255}.
FT   REGION     4029   4426       Adenylation 4. {ECO:0000255}.
FT   REGION     4669   4948       Condensation 5. {ECO:0000255}.
FT   MOD_RES     768    768       O-(pantetheine 4'-phosphoryl)serine.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00258}.
FT   MOD_RES    2376   2376       O-(pantetheine 4'-phosphoryl)serine.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00258}.
FT   MOD_RES    3500   3500       O-(pantetheine 4'-phosphoryl)serine.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00258}.
FT   MOD_RES    4592   4592       O-(pantetheine 4'-phosphoryl)serine.
FT                                {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
//