FTMA_ASPFU
ID FTMA_ASPFU Reviewed; 2211 AA.
AC Q4WAW3;
DT 18-APR-2012, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2005, sequence version 1.
DT 25-MAY-2022, entry version 109.
DE RecName: Full=Nonribosomal peptide synthetase 13 {ECO:0000303|PubMed:16962256};
DE EC=6.3.3.- {ECO:0000269|PubMed:16755625};
DE AltName: Full=Brevianamide F synthase {ECO:0000303|PubMed:16755625};
DE AltName: Full=Fumitremorgin biosynthesis protein A {ECO:0000303|PubMed:16755625};
GN Name=NRPS13 {ECO:0000303|PubMed:16962256};
GN Synonyms=ftmA {ECO:0000303|PubMed:16755625}, pesN; ORFNames=AFUA_8G00170;
OS Neosartorya fumigata (strain ATCC MYA-4609 / Af293 / CBS 101355 / FGSC
OS A1100) (Aspergillus fumigatus).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Aspergillaceae; Aspergillus;
OC Aspergillus subgen. Fumigati.
OX NCBI_TaxID=330879;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC MYA-4609 / Af293 / CBS 101355 / FGSC A1100;
RX PubMed=16372009; DOI=10.1038/nature04332;
RA Nierman W.C., Pain A., Anderson M.J., Wortman J.R., Kim H.S., Arroyo J.,
RA Berriman M., Abe K., Archer D.B., Bermejo C., Bennett J.W., Bowyer P.,
RA Chen D., Collins M., Coulsen R., Davies R., Dyer P.S., Farman M.L.,
RA Fedorova N., Fedorova N.D., Feldblyum T.V., Fischer R., Fosker N.,
RA Fraser A., Garcia J.L., Garcia M.J., Goble A., Goldman G.H., Gomi K.,
RA Griffith-Jones S., Gwilliam R., Haas B.J., Haas H., Harris D.E.,
RA Horiuchi H., Huang J., Humphray S., Jimenez J., Keller N., Khouri H.,
RA Kitamoto K., Kobayashi T., Konzack S., Kulkarni R., Kumagai T., Lafton A.,
RA Latge J.-P., Li W., Lord A., Lu C., Majoros W.H., May G.S., Miller B.L.,
RA Mohamoud Y., Molina M., Monod M., Mouyna I., Mulligan S., Murphy L.D.,
RA O'Neil S., Paulsen I., Penalva M.A., Pertea M., Price C., Pritchard B.L.,
RA Quail M.A., Rabbinowitsch E., Rawlins N., Rajandream M.A., Reichard U.,
RA Renauld H., Robson G.D., Rodriguez de Cordoba S., Rodriguez-Pena J.M.,
RA Ronning C.M., Rutter S., Salzberg S.L., Sanchez M., Sanchez-Ferrero J.C.,
RA Saunders D., Seeger K., Squares R., Squares S., Takeuchi M., Tekaia F.,
RA Turner G., Vazquez de Aldana C.R., Weidman J., White O., Woodward J.R.,
RA Yu J.-H., Fraser C.M., Galagan J.E., Asai K., Machida M., Hall N.,
RA Barrell B.G., Denning D.W.;
RT "Genomic sequence of the pathogenic and allergenic filamentous fungus
RT Aspergillus fumigatus.";
RL Nature 438:1151-1156(2005).
RN [2]
RP FUNCTION.
RX PubMed=16000710; DOI=10.1099/mic.0.27962-0;
RA Grundmann A., Li S.M.;
RT "Overproduction, purification and characterization of FtmPT1, a
RT brevianamide F prenyltransferase from Aspergillus fumigatus.";
RL Microbiology 151:2199-2207(2005).
RN [3]
RP INDUCTION.
RX PubMed=16207816; DOI=10.1091/mbc.e05-07-0617;
RA Sheppard D.C., Doedt T., Chiang L.Y., Kim H.S., Chen D., Nierman W.C.,
RA Filler S.G.;
RT "The Aspergillus fumigatus StuA protein governs the up-regulation of a
RT discrete transcriptional program during the acquisition of developmental
RT competence.";
RL Mol. Biol. Cell 16:5866-5879(2005).
RN [4]
RP FUNCTION, CATALYTIC ACTIVITY, AND PATHWAY.
RX PubMed=16755625; DOI=10.1002/cbic.200600003;
RA Maiya S., Grundmann A., Li S.M., Turner G.;
RT "The fumitremorgin gene cluster of Aspergillus fumigatus: identification of
RT a gene encoding brevianamide F synthetase.";
RL ChemBioChem 7:1062-1069(2006).
RN [5]
RP NOMENCLATURE.
RX PubMed=16962256; DOI=10.1016/j.gene.2006.07.008;
RA Cramer R.A. Jr., Stajich J.E., Yamanaka Y., Dietrich F.S., Steinbach W.J.,
RA Perfect J.R.;
RT "Phylogenomic analysis of non-ribosomal peptide synthetases in the genus
RT Aspergillus.";
RL Gene 383:24-32(2006).
RN [6]
RP REVIEW ON FUNCTION, AND DOMAIN.
RX PubMed=17464044; DOI=10.1099/mic.0.2006/006908-0;
RA Stack D., Neville C., Doyle S.;
RT "Nonribosomal peptide synthesis in Aspergillus fumigatus and other fungi.";
RL Microbiology 153:1297-1306(2007).
RN [7]
RP FUNCTION.
RX PubMed=18683158; DOI=10.1002/cbic.200800240;
RA Grundmann A., Kuznetsova T., Afiyatullov S.S., Li S.M.;
RT "FtmPT2, an N-prenyltransferase from Aspergillus fumigatus, catalyses the
RT last step in the biosynthesis of fumitremorgin B.";
RL ChemBioChem 9:2059-2063(2008).
RN [8]
RP FUNCTION.
RX PubMed=19226505; DOI=10.1002/cbic.200800787;
RA Kato N., Suzuki H., Takagi H., Asami Y., Kakeya H., Uramoto M., Usui T.,
RA Takahashi S., Sugimoto Y., Osada H.;
RT "Identification of cytochrome P450s required for fumitremorgin biosynthesis
RT in Aspergillus fumigatus.";
RL ChemBioChem 10:920-928(2009).
RN [9]
RP FUNCTION.
RX PubMed=19763315; DOI=10.1039/b908392h;
RA Steffan N., Grundmann A., Afiyatullov S., Ruan H., Li S.M.;
RT "FtmOx1, a non-heme Fe(II) and alpha-ketoglutarate-dependent dioxygenase,
RT catalyses the endoperoxide formation of verruculogen in Aspergillus
RT fumigatus.";
RL Org. Biomol. Chem. 7:4082-4087(2009).
RN [10]
RP FUNCTION.
RX PubMed=21105662; DOI=10.1021/ja106817c;
RA Jost M., Zocher G., Tarcz S., Matuschek M., Xie X., Li S.M., Stehle T.;
RT "Structure-function analysis of an enzymatic prenyl transfer reaction
RT identifies a reaction chamber with modifiable specificity.";
RL J. Am. Chem. Soc. 132:17849-17858(2010).
RN [11]
RP FUNCTION.
RX PubMed=23090579; DOI=10.1039/c2ob26149a;
RA Wollinsky B., Ludwig L., Xie X., Li S.M.;
RT "Breaking the regioselectivity of indole prenyltransferases: identification
RT of regular C3-prenylated hexahydropyrrolo[2,3-b]indoles as side products of
RT the regular C2-prenyltransferase FtmPT1.";
RL Org. Biomol. Chem. 10:9262-9270(2012).
RN [12]
RP FUNCTION, AND PATHWAY.
RX PubMed=23649274; DOI=10.1271/bbb.130026;
RA Kato N., Suzuki H., Okumura H., Takahashi S., Osada H.;
RT "A point mutation in ftmD blocks the fumitremorgin biosynthetic pathway in
RT Aspergillus fumigatus strain Af293.";
RL Biosci. Biotechnol. Biochem. 77:1061-1067(2013).
CC -!- FUNCTION: Nonribosomal peptide synthetase; part of the gene cluster
CC that mediates the biosynthesis of fumitremorgins, indole alkaloids that
CC carry not only intriguing chemical structures, but also interesting
CC biological and pharmacological activities (PubMed:16755625,
CC PubMed:23649274). The biosynthesis of fumitremorgin-type alkaloids
CC begins by condensation of the two amino acids L-tryptophan and L-
CC proline to brevianamide F, catalyzed by the non-ribosomal peptide
CC synthetase ftmA (PubMed:16755625, PubMed:17464044). Brevianamide F is
CC then prenylated by the prenyltransferase ftmPT1/ftmB in the presence of
CC dimethylallyl diphosphate, resulting in the formation of tryprostatin B
CC (PubMed:16000710, PubMed:21105662, PubMed:23090579). The three
CC cytochrome P450 monooxygenases, ftmP450-1/ftmC, ftmP450-2/ftmE and
CC ftmP450-3/FtmG, are responsible for the conversion of tryprostatin B to
CC 6-hydroxytryprostatin B, tryprostatin A to fumitremorgin C and
CC fumitremorgin C to 12,13-dihydroxyfumitremorgin C, respectively
CC (PubMed:19226505). The putative methyltransferase ftmMT/ftmD is
CC expected for the conversion of 6-hydroxytryprostatin B to tryprostatin
CC A (Probable). FtmPT2/FtmH catalyzes the prenylation of 12,13-
CC dihydroxyfumitre-morgin C in the presence of dimethylallyl diphosphate,
CC resulting in the formation of fumitremorgin B (PubMed:18683158).
CC Fumitremorgin B is further converted to verruculogen by ftmOx1/ftmF via
CC the insertion of an endoperoxide bond between the two prenyl moieties
CC (PubMed:19763315). In some fungal species, verruculogen is further
CC converted to fumitremorgin A, but the enzymes involved in this step
CC have not been identified yet (Probable). {ECO:0000269|PubMed:16000710,
CC ECO:0000269|PubMed:16755625, ECO:0000269|PubMed:17464044,
CC ECO:0000269|PubMed:18683158, ECO:0000269|PubMed:19226505,
CC ECO:0000269|PubMed:19763315, ECO:0000269|PubMed:21105662,
CC ECO:0000269|PubMed:23090579, ECO:0000269|PubMed:23649274, ECO:0000305,
CC ECO:0000305|PubMed:16000710}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2 ATP + L-proline + L-tryptophan = 2 AMP + brevianamide F + 2
CC diphosphate + 2 H(+); Xref=Rhea:RHEA:35935, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:33019, ChEBI:CHEBI:57912,
CC ChEBI:CHEBI:60039, ChEBI:CHEBI:64530, ChEBI:CHEBI:456215;
CC Evidence={ECO:0000269|PubMed:16755625};
CC -!- PATHWAY: Mycotoxin biosynthesis. {ECO:0000269|PubMed:16755625,
CC ECO:0000269|PubMed:23649274}.
CC -!- INDUCTION: Expression is under the control of StuA, which is
CC responsible for transcriptional activation during acquisition of
CC developmental competence. {ECO:0000269|PubMed:16207816}.
CC -!- DOMAIN: NRP synthetases are composed of discrete domains (adenylation
CC (A), thiolation (T) or peptidyl carrier protein (PCP) and condensation
CC (C) domains) which when grouped together are referred to as a single
CC module. Each module is responsible for the recognition (via the A
CC domain) and incorporation of a single amino acid into the growing
CC peptide product. Thus, an NRP synthetase is generally composed of one
CC or more modules and can terminate in a thioesterase domain (TE) that
CC releases the newly synthesized peptide from the enzyme. Occasionally,
CC epimerase (E) domains (responsible for l- to d- amino acid conversion)
CC are present within the NRP synthetase. NRPS13 has the following
CC architecture: A-T-C-A-T-C. {ECO:0000305|PubMed:17464044}.
CC -!- SIMILARITY: Belongs to the NRP synthetase family. {ECO:0000305}.
CC -!- CAUTION: In contrast to other A.fumigatus strains, strain ATCC MYA-4609
CC does not produce indole alkaloids such as fumitremorgins and
CC verruculogen. While the biosynthetic pathway is complete, a variation
CC in the O-methyltransferase FtmD (AC Q4WAW6) abolishes production of the
CC tryprostatin A intermediate (PubMed:23649274).
CC {ECO:0000305|PubMed:23649274}.
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DR EMBL; AAHF01000014; EAL85149.1; -; Genomic_DNA.
DR RefSeq; XP_747187.1; XM_742094.1.
DR AlphaFoldDB; Q4WAW3; -.
DR SMR; Q4WAW3; -.
DR STRING; 746128.CADAFUBP00008414; -.
DR EnsemblFungi; EAL85149; EAL85149; AFUA_8G00170.
DR GeneID; 3504405; -.
DR KEGG; afm:AFUA_8G00170; -.
DR VEuPathDB; FungiDB:Afu8g00170; -.
DR eggNOG; KOG1178; Eukaryota.
DR eggNOG; KOG1256; Eukaryota.
DR HOGENOM; CLU_000022_60_2_1; -.
DR InParanoid; Q4WAW3; -.
DR OMA; AEACNFQ; -.
DR OrthoDB; 4243at2759; -.
DR Proteomes; UP000002530; Chromosome 8.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
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; IBA:GO_Central.
DR GO; GO:0043041; P:amino acid activation for nonribosomal peptide biosynthetic process; IBA:GO_Central.
DR GO; GO:1900805; P:brevianamide F biosynthetic process; IMP:AspGD.
DR GO; GO:1900772; P:fumitremorgin B biosynthetic process; IDA:AspGD.
DR GO; GO:0019184; P:nonribosomal peptide biosynthetic process; ISM:AspGD.
DR GO; GO:0044550; P:secondary metabolite biosynthetic process; IBA:GO_Central.
DR GO; GO:1902181; P:verruculogen biosynthetic process; IDA:GO_Central.
DR Gene3D; 1.10.1200.10; -; 2.
DR Gene3D; 3.30.300.30; -; 2.
DR Gene3D; 3.30.559.10; -; 2.
DR Gene3D; 3.40.50.12780; -; 2.
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; IPR009081; PP-bd_ACP.
DR InterPro; IPR006162; Ppantetheine_attach_site.
DR Pfam; PF00501; AMP-binding; 2.
DR Pfam; PF00668; Condensation; 2.
DR Pfam; PF00550; PP-binding; 2.
DR SUPFAM; SSF47336; SSF47336; 2.
DR TIGRFAMs; TIGR01733; AA-adenyl-dom; 1.
DR PROSITE; PS00455; AMP_BINDING; 2.
DR PROSITE; PS50075; CARRIER; 2.
DR PROSITE; PS00012; PHOSPHOPANTETHEINE; 2.
PE 1: Evidence at protein level;
KW Isomerase; Ligase; Phosphopantetheine; Phosphoprotein; Reference proteome;
KW Repeat; Virulence.
FT CHAIN 1..2211
FT /note="Nonribosomal peptide synthetase 13"
FT /id="PRO_0000416554"
FT DOMAIN 594..671
FT /note="Carrier 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT DOMAIN 1677..1756
FT /note="Carrier 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT REGION 76..475
FT /note="Adenylation 1"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:17464044"
FT REGION 710..975
FT /note="Condensation 1"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:17464044"
FT REGION 1169..1563
FT /note="Adenylation 2"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:17464044"
FT REGION 1814..2069
FT /note="Condensation 2"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:17464044"
FT MOD_RES 631
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT MOD_RES 1714
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
SQ SEQUENCE 2211 AA; 242838 MW; 3173AE2D3F157D9F CRC64;
MAMALAVGAP SEQRGNLPYN TLKDGPTVDS MKATTDGKNG QGESAFWDTC VHTVFREHCQ
RAPNSPAVNA WDGSFTYAEL DSLSDAIASV LILSGVGPES IIPIYMQKSR WTTVAILGVL
KSGGAFTLLD PSHPRSRVEE ISKEIQARFI LTSEKLSKQC LEMFSVLVVE HLSRACLPSP
GQAGHTRSRP ENAAYIAFTS GSTGKPKGIV IEHRSYCSGA RSHLKVFGID STSRVLQFAS
YAFDVSIMET LSTLMAGGCL CVMSESERSD PNLFVVSYKN LRISHCFMTP SFARTVPWTE
CCNPPPTLIV GGELMRPSDA RAYKEMGIRC MNAYGPAECS VNVSVQSRVE AAVDPRNIGY
TTGATAWIIS PENPEELMPT GTVGELLVEG PIVGRGYLND PKATRQAFID TPAWLRRHRK
GTSYQHRVYR TGDLASLDSI TGALLLHGRK DAQVKIRGQR VELPDIEHHL QLTLPNDNAE
VIVEKVTFSD DGSEKLIAFV LVRPSNTDSV IGNTGDRLFL APQSQIMEQF AISKKHLQTH
LPSYMVPDIF IPISTLPQTA SGKTDRKALR TRAAALSRRD VQCFLLSPAG GKRPPSTPKE
ATIRSLYSNV LNLPIDLIGM DDTFLRLGGD SLQAIRLVAA ARAAGLILQA KDILSSQSTL
AEQSKRAGLI QTIDRTWESS PPFALLHGPT RHAIVDLAQK QCRVPSNLIE DIYPCTALQE
GMFITSLKHP GMYTGQIIFD IPDRMELPRL RAAWLSVVSE NAALRTRIIE THEGLMQAVI
VDDFVWEEET DEMLLSSDGE ALEITKIGVP LVRFRYRPRH RQLMMTIHHS IWDGWSLRLV
HEQLHRAYIG RDLLPSTSYR SFIQYTQELQ GADEFWASEL AGVNAPIFPT LPSGNYRPRV
NASHRHVVRN LASTGKEEHT AATYIHLAWS LLVAHYTDAD ETVYGVTVNG RSADVPGVEN
IVGPTIATVP TRIRVNEEDT VEMALDHVQD ALARMIPYEQ AGLQRISRCS RDASEACRFQ
TLLIIEAPTD SDVDCEKNEA GNFSIIGGTT QTGMDYTAFS SYAMMLVFRT SANKSAISFD
ITYDAQVIGH DEVERMAHQF EHVLRHIYTL ATGRIGDISF IGPRDIEQVQ QWNSSMPPAD
NRFLQELIFA QCSRRPQASA IISWDGSWTY RELWAHSSFF ARQLQRYGVT RGTPVAVCLD
RSRWSIAVIL GVLLARGTCV LIDLLAPRQR VRDILQIAGT GILVHSHATA TLTSGLCPTV
VNVSFLAAQS DSSQPEFPFT LETWGGTPED LAFIIFTSGS TGHPKGIEMP HRTLSTSISH
HSAGMRVTSS SRVLHFSSYA FDVSIYEIFT TLAAGGTICV PSEFDRMNNL AGFIQDTQVN
WAFLTPSTAR SLNPADVPLL TTLVLGGEAV THESVEVWAK GRSLINGYGP AEATICGVGN
IPEAGWKSGV VGRIIGGLGW VTVPSDPNRL AAVGAVGELL LEGPFLARGY LNLPEVTKAA
FIDPPSWRTR IPAPSPYSFL YRTGDLVRYQ PDGSIQYVGR KDSRVKLRGQ LVDLGAVEAS
VMRVYPAAGQ VVADVLVSEN TARLIAMVKL GPSVTENHDG PMFAAPDLVF NEAAASIQAR
LRAIVPAYMV PSMFIPLRHI PRTLTGKTDR RRLRDKILSL SHSDLQRYMM SSSTKTPMSD
DNERRLQEIW AEVLQLPCEA IGREDSFLSL GGESLATMKM VALARRVGFM FAVTDVMNNT
SLSTLARSRH LITEQAILTS SPSLSLPTIE GESLQEILRP LLNAGHIQGG NDIAAIHPVT
AAQAFLVQRY PWSHFQFDLS GAVSPSKLQT ACTALMARFT ILRTVFVEHA GCLLQLVLRE
VPNRVHEITT NEPLDDFCNS VCQQQQDVCV VNSTTLPTLF TLVSNRQLNR HRLLLRLAHA
QYDLTTIPLI VQSLADEYNR TLRSGFSADF GYYLSHHKRQ NNDDRSHNFW KRYLSGSSMM
STNQTADPTT VQERVFHVTG SCIIIPTSHP PDITIATAVK AAVCLVLAAR TGCTDIVIGQ
TVDARCSSAD STLDQIVGPC TNYIPYRLSV CCSKTALEYL RSAQAQHTTC LRYSSLDFDQ
IVAKCTSWPS STQFGYIVQH QDTGAELALT LGGDTTSLPM TSYGRVFPQG EVWIGSTPCS
TGLRIDVIAL SAVLSQKDAQ TMAEEVGAAL EKLLGCGYRR LSHLIGNTFA T
