FTMA_ASPFM
ID FTMA_ASPFM Reviewed; 2211 AA.
AC B9WZX0;
DT 16-OCT-2013, integrated into UniProtKB/Swiss-Prot.
DT 14-APR-2009, sequence version 1.
DT 03-AUG-2022, entry version 61.
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};
OS Neosartorya fumigata (Aspergillus fumigatus).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Aspergillaceae; Aspergillus;
OC Aspergillus subgen. Fumigati.
OX NCBI_TaxID=746128;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND FUNCTION.
RC STRAIN=BM939;
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 [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=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 [9]
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 [10]
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 [11]
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}.
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DR EMBL; AB436628; BAH23995.1; -; Genomic_DNA.
DR AlphaFoldDB; B9WZX0; -.
DR SMR; B9WZX0; -.
DR BioCyc; MetaCyc:MON-18761; -.
DR GO; GO:0016853; F:isomerase activity; IEA:UniProtKB-KW.
DR GO; GO:0016874; F:ligase activity; IEA:UniProtKB-KW.
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 Alkaloid metabolism; Isomerase; Ligase; Phosphopantetheine; Phosphoprotein;
KW Repeat; Virulence.
FT CHAIN 1..2211
FT /note="Nonribosomal peptide synthetase 13"
FT /id="PRO_0000424109"
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; 242786 MW; 1E275CDC515B5618 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 ARAAGLILHA KDILSSQSTL
AEQSKRAGLI QTIDRTWESS PPFALLHGPT RHAIVDLAQK QCRVPSNLIE DIYPCTALQE
GMFITSLKHP GMYTGQIIFD IPDRMELPRL KAAWLSVVSE NAALRTRIIE THEGLMQAVI
VDDFVWEEET DEMLLSSDGE ALEITKIGVP LVRFRYRPRH RQLMMTIHHS IWDGWSLRLV
HEQLQRAYIG RDLLPSTSYR SFIQYTQELP GADEFWASEL AGVNAPIFPT LPSGNYRPRV
NASHRHVVRN LASTGKEEHT AATYIHLAWS LLVAHYTDAD ETVYGVTVNG RSADVPGIEN
IVGPTIATVP TRIRVNEEDT VEMALDHVQD ALARMIPYEQ AGLQRISRCS RDASEACRFQ
NLLIIEAPTD SDVDCEKNEA GNFSIIGGTT QTGMDYTAFS SYAMMLVFRT SANKSAISFD
ITYDAQVIGH DEVERMAHQF EHVLRHIYTL ATGRIGDISF IGPRDIEQVQ QWNSSMPPAD
NRFLQELIFA QCSRRPQASA IISWDGSWTY RELWAHSSFF ARQLQRYGVT RGTPVAVCLD
RSRWSIAVIL GVLLARGTCV LIDLLAPRQR VRDILQIAGT GILVHSHATA TLTSGLCPTV
INVSFLAAQS 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 LRYSSLDLDQ
IVAKCTSWPS STQFGYIVQH QDTGAELALT LGGDTTSLPM TSYGRVFPQG EVWIGSTPCS
TGLRIDVIAL SAVLSQKDAQ TMAEEVGAAL EKLLGCGYRR LSHLIGNTFA T
