ID   FTMA_NEOFI              Reviewed;        2212 AA.
AC   A1DA59;
DT   16-OCT-2013, integrated into UniProtKB/Swiss-Prot.
DT   23-JAN-2007, sequence version 1.
DT   25-MAY-2022, entry version 88.
DE   RecName: Full=Nonribosomal peptide synthetase ftmPS {ECO:0000303|PubMed:23109474};
DE            EC=6.3.3.- {ECO:0000250|UniProtKB:Q4WAW3};
DE   AltName: Full=Brevianamide F synthase {ECO:0000303|PubMed:23109474};
DE   AltName: Full=Fumitremorgin biosynthesis protein A {ECO:0000250|UniProtKB:Q4WAW3};
GN   Name=ftmPS; Synonyms=ftmA {ECO:0000250|UniProtKB:Q4WAW3};
GN   ORFNames=NFIA_093690;
OS   Neosartorya fischeri (strain ATCC 1020 / DSM 3700 / CBS 544.65 / FGSC A1164
OS   / JCM 1740 / NRRL 181 / WB 181) (Aspergillus fischerianus).
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC   Eurotiomycetidae; Eurotiales; Aspergillaceae; Aspergillus;
OC   Aspergillus subgen. Fumigati.
OX   NCBI_TaxID=331117;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC 1020 / DSM 3700 / CBS 544.65 / FGSC A1164 / JCM 1740 / NRRL 181
RC   / WB 181;
RX   PubMed=18404212; DOI=10.1371/journal.pgen.1000046;
RA   Fedorova N.D., Khaldi N., Joardar V.S., Maiti R., Amedeo P., Anderson M.J.,
RA   Crabtree J., Silva J.C., Badger J.H., Albarraq A., Angiuoli S., Bussey H.,
RA   Bowyer P., Cotty P.J., Dyer P.S., Egan A., Galens K., Fraser-Liggett C.M.,
RA   Haas B.J., Inman J.M., Kent R., Lemieux S., Malavazi I., Orvis J.,
RA   Roemer T., Ronning C.M., Sundaram J.P., Sutton G., Turner G., Venter J.C.,
RA   White O.R., Whitty B.R., Youngman P., Wolfe K.H., Goldman G.H.,
RA   Wortman J.R., Jiang B., Denning D.W., Nierman W.C.;
RT   "Genomic islands in the pathogenic filamentous fungus Aspergillus
RT   fumigatus.";
RL   PLoS Genet. 4:E1000046-E1000046(2008).
RN   [2]
RP   IDENTIFICATION, AND FUNCTION.
RX   PubMed=23109474; DOI=10.1002/cbic.201200523;
RA   Mundt K., Wollinsky B., Ruan H.L., Zhu T., Li S.M.;
RT   "Identification of the verruculogen prenyltransferase FtmPT3 by a
RT   combination of chemical, bioinformatic and biochemical approaches.";
RL   ChemBioChem 13:2583-2592(2012).
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:23109474). The
CC       biosynthesis of fumitremorgin-type alkaloids begins by condensation of
CC       the two amino acids L-tryptophan and L-proline to brevianamide F,
CC       catalyzed by the non-ribosomal peptide synthetase ftmPS/ftmA (By
CC       similarity). Brevianamide F is then prenylated by the prenyltransferase
CC       ftmPT1/ftmB in the presence of dimethylallyl diphosphate, resulting in
CC       the formation of tryprostatin B (By similarity). The three cytochrome
CC       P450 monooxygenases, ftmP450-1/ftmC, ftmP450-2/ftmE and ftmP450-3/FtmG,
CC       are responsible for the conversion of tryprostatin B to 6-
CC       hydroxytryprostatin B, tryprostatin A to fumitremorgin C and
CC       fumitremorgin C to 12,13-dihydroxyfumitremorgin C, respectively (By
CC       similarity). The putative methyltransferase ftmMT/ftmD is expected for
CC       the conversion of 6-hydroxytryprostatin B to tryprostatin A (By
CC       similarity). 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 (By similarity).
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       (By similarity). Finally, verruculogen is further converted to
CC       fumitremorgin A by the verruculogen prenyltransferase ftmPT3
CC       (PubMed:23109474). {ECO:0000250|UniProtKB:Q4WAW3,
CC       ECO:0000269|PubMed:23109474}.
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:0000250|UniProtKB:Q4WAW3};
CC   -!- PATHWAY: Mycotoxin biosynthesis. {ECO:0000250|UniProtKB:Q4WAW3}.
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:0000250|UniProtKB:Q4WAW3}.
CC   -!- SIMILARITY: Belongs to the NRP synthetase family. {ECO:0000305}.
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DR   EMBL; DS027694; EAW19749.1; -; Genomic_DNA.
DR   RefSeq; XP_001261646.1; XM_001261645.1.
DR   AlphaFoldDB; A1DA59; -.
DR   SMR; A1DA59; -.
DR   STRING; 36630.CADNFIAP00008991; -.
DR   EnsemblFungi; EAW19749; EAW19749; NFIA_093690.
DR   GeneID; 4588679; -.
DR   KEGG; nfi:NFIA_093690; -.
DR   VEuPathDB; FungiDB:NFIA_093690; -.
DR   eggNOG; KOG1176; Eukaryota.
DR   eggNOG; KOG1178; Eukaryota.
DR   HOGENOM; CLU_000022_60_2_1; -.
DR   OMA; AEACNFQ; -.
DR   OrthoDB; 4243at2759; -.
DR   Proteomes; UP000006702; Unassembled WGS sequence.
DR   GO; GO:0016853; F:isomerase activity; IEA:UniProtKB-KW.
DR   GO; GO:0016874; F:ligase activity; IEA:UniProtKB-KW.
DR   GO; GO:0009820; P:alkaloid metabolic process; IEA:UniProtKB-KW.
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   3: Inferred from homology;
KW   Alkaloid metabolism; Isomerase; Ligase; Phosphopantetheine; Phosphoprotein;
KW   Reference proteome; Repeat; Virulence.
FT   CHAIN           1..2212
FT                   /note="Nonribosomal peptide synthetase ftmPS"
FT                   /id="PRO_0000424110"
FT   DOMAIN          592..669
FT                   /note="Carrier 1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT   DOMAIN          1678..1757
FT                   /note="Carrier 2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT   REGION          74..473
FT                   /note="Adenylation 1"
FT                   /evidence="ECO:0000250|UniProtKB:Q4WAW3, ECO:0000255"
FT   REGION          708..973
FT                   /note="Condensation 1"
FT                   /evidence="ECO:0000250|UniProtKB:Q4WAW3, ECO:0000255"
FT   REGION          1167..1564
FT                   /note="Adenylation 2"
FT                   /evidence="ECO:0000250|UniProtKB:Q4WAW3, ECO:0000255"
FT   REGION          1815..2070
FT                   /note="Condensation 2"
FT                   /evidence="ECO:0000250|UniProtKB:Q4WAW3, ECO:0000255"
FT   MOD_RES         629
FT                   /note="O-(pantetheine 4'-phosphoryl)serine"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT   MOD_RES         1715
FT                   /note="O-(pantetheine 4'-phosphoryl)serine"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
SQ   SEQUENCE   2212 AA;  243037 MW;  C9D15E93498A456D CRC64;
     MALAVAAPSE WRGILPYNTS KDSPTVHSMK VATDVKNEQG EFGFWDTCVH TVVREHCQRS
     PDSPAVNAWD GSFTYAELDS LSDAIASVLI LFGVKPESII PIYMHKSRWT TVAILGVLKS
     GGAFTLLDPS HPRSRLEEIC KEIQARFILT SEELSKQCSE MSSVLVVEHL SRACLLSPGQ
     AGQTPSRPEN AAYIAFTSGS TGKPKGIVIE HRSYCSGARS HLKVFGIDST SRVLQFASYA
     FDVSIMETLS TLMAGGCLCV MSESERSDPN LFVESYKNFR ISHCFMTPSF ARTVQWTECC
     NPPPTLIVGG ELMRPSDTRA YKAMGICCMN AYGPAECSVN VSVQSRVEDG VDPRNIGYTT
     GATAWIISPE NPEQLMPPGT VGELLVEGPI VGRGYLNDPS ATRQAFIDTP GWLRRHRKGT
     SYQHRVYRTG DLASQDSISG ALLLHGRKDA QVKIRGQRVE LPDIEHHLQQ TLPDGDAEVI
     VEKVTFSDDG AEKLIAFVLI PPSSTGFITD NMGDRLFLAP QSQIMEQFAI SKKHLQTNLP
     SYMVPDIFIP ISTIPQTVSG KTDRKALRTR AAALSRRDVQ CYLLSPTGDK RPPSTLKETT
     IRSLYSKVLN LPIDLIGMDD TFLRLGGDSL QAIRLVAAAR TAGLVLHAKD ILSSQSTLAE
     QSQRAGLIQT SDHTGEASTP FALLPVATRH DIVDLAQKQC RVSSKLIEDI YPCTALQEGM
     FMTSLRHPGM YTGQITFDIP DRMELPRLRA AWLSVVSKNA ALRTRIIETH EGLMQAVIVD
     DFAWEEETDE MLPSGRWEVL EITKIGVPLV RFRYRPRHRQ LIMTIHHSIW DGWSLRLVHE
     QLQRAYIGRD PLPSTSYRSF IQYGQDLPGA DEFWASELAG VNAPIFPTLP SGNYRPCVNA
     SHRHGVRKLV STGRGEHTAA TYIHLAWSLL VAHYTDADET VYGVTVNGRS ADVPGIENIV
     GPTIATVPLR IRVNQEDTVK MALDQVQDSL ARMIPYEQAG LQRISRCSRD ASEACRFQTL
     LIIEAPADRD VACEKNEAKN FSIIRGTTQT GMDYTAFSPY AMMLIFRTSA DKSAITLDIT
     YDAQVIGCVE VERMAHQFEH VLRHIYKRAT GRIGDISFLG PRDIEQVQQW NSYMPPADNR
     FLQELIFARC SRRPQASAII SWDGSWTYRE LWAHSSFFAR QLQRYGVTRG TPVAVCLDRS
     RWSIAVILAV LLAGGTCVLI DLLSPRQRVR DILQIVGAGI MVNSHATAPV TSGLCPTVID
     VSLLVAQNDD SQTECPFNLD TWERGVGTPE DLAFIMFTSG STGHPKGIEM PHRTLSTSIY
     HHSAGMKVKS SSRVLHFSSY AFDVSIYEIF TTLAAGGTIC VPSEFDRMNN LSGFIQDTQV
     NWAFLTPSTA RSLDPADVPL LTTLVLGGEA VTHESVEAWA KGRSLINGYG PAEATICGVG
     NIPEAGWKSG VIGQIVGGLG WVTVPSDPNR LAAVGAVGEL LLEGPFLARG YLNLPEVTRA
     AFIDPPSWRT QIPAPSPYPF LYRTGDLVQY QPDGSIQYIG RKDSRIKLRG QLVDLSAVEA
     SLMRVYPAAI QVVADVLVSE NTTRLIAMMK LGPPVTETHD DPLFEAPDLA FNEAAASVQA
     RLRAIVPPYM VPSMFIPLRH IPRTLTGKTD RRQLRDKLLS LSQSDLQRYI MSSSAKTPMS
     DDNERRLQEI WAEVLQLPCE AIGREDSFLL LGGESLATMK MVALARRVGF VFAVADVLNN
     TSLSTLAQFR HLITEDDIPS PSPSLSLSTI ESQSLQKILR PLQNGGLIQG GNDIAAIHPV
     TAAQAFLVQR YPWSHFQFDL SGAISPSKLQ TACTTLMARF TILRTVFVEH AGHLLQLVLR
     EVRKCVHEIT TDEPLDDFCN SLCQQQQGVC VVNSTALPTL FTLVSNRQLN RHRLLLRLAH
     AQYDLTTIPL IVQALADEYN GTLRAGFSSD FSYYLNHHMR QTNDDRAHTF WNQYLSGSFM
     TSTDQTADTT TPQERIFHVT GSCTVTPASH PLGITTATAV KAAVCLVLAS RTGCTDIVVG
     QTVDARCSSA DGTLDQIVGP CTNYIPYRLS VCCSKTALEY LCSAQAQHTT SLRYSSLDLD
     QIVAKCTSWP SSTQFGYIVQ HQNTGADLAL SLAGCTTSSP MTSYGHVFPQ GEVWIGSTPY
     STGLKIDVIA PSAVLSQEDA QAMAGEVGAA LENLLACGDR PLSDLIGNTF AT