ID   SIDE_ASPFU              Reviewed;        2109 AA.
AC   Q4WF61;
DT   18-APR-2012, integrated into UniProtKB/Swiss-Prot.
DT   17-APR-2007, sequence version 2.
DT   25-MAY-2022, entry version 105.
DE   RecName: Full=Nonribosomal peptide synthase sidE {ECO:0000303|PubMed:15953695};
DE            Short=NPRS sidE {ECO:0000303|PubMed:15953695};
DE            EC=6.3.2.- {ECO:0000305|PubMed:17845073};
DE   AltName: Full=Siderophore synthetase E {ECO:0000303|PubMed:17464044};
GN   Name=NRPS3 {ECO:0000303|PubMed:16962256};
GN   Synonyms=sidE {ECO:0000303|PubMed:15953695}; ORFNames=AFUA_3G03350;
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=15504822; DOI=10.1084/jem.20041242;
RA   Schrettl M., Bignell E., Kragl C., Joechl C., Rogers T., Arst H.N. Jr.,
RA   Haynes K., Haas H.;
RT   "Siderophore biosynthesis but not reductive iron assimilation is essential
RT   for Aspergillus fumigatus virulence.";
RL   J. Exp. Med. 200:1213-1219(2004).
RN   [3]
RP   FUNCTION.
RC   STRAIN=NIH 5233 / ATCC 13073;
RX   PubMed=16113265; DOI=10.1128/iai.73.9.5493-5503.2005;
RA   Hissen A.H., Wan A.N., Warwas M.L., Pinto L.J., Moore M.M.;
RT   "The Aspergillus fumigatus siderophore biosynthetic gene sidA, encoding L-
RT   ornithine N(5)-oxygenase, is required for virulence.";
RL   Infect. Immun. 73:5493-5503(2005).
RN   [4]
RP   DOMAIN, INDUCTION, AND FUNCTION.
RX   PubMed=15953695; DOI=10.1016/j.femsle.2005.05.028;
RA   Reiber K., Reeves E.P., Neville C.M., Winkler R., Gebhardt P., Kavanagh K.,
RA   Doyle S.;
RT   "The expression of selected non-ribosomal peptide synthetases in
RT   Aspergillus fumigatus is controlled by the availability of free iron.";
RL   FEMS Microbiol. Lett. 248:83-91(2005).
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=17845073; DOI=10.1371/journal.ppat.0030128;
RA   Schrettl M., Bignell E., Kragl C., Sabiha Y., Loss O., Eisendle M.,
RA   Wallner A., Arst H.N. Jr., Haynes K., Haas H.;
RT   "Distinct roles for intra- and extracellular siderophores during
RT   Aspergillus fumigatus infection.";
RL   PLoS Pathog. 3:1195-1207(2007).
RN   [8]
RP   INDUCTION.
RX   PubMed=18721228; DOI=10.1111/j.1365-2958.2008.06376.x;
RA   Schrettl M., Kim H.S., Eisendle M., Kragl C., Nierman W.C., Heinekamp T.,
RA   Werner E.R., Jacobsen I., Illmer P., Yi H., Brakhage A.A., Haas H.;
RT   "SreA-mediated iron regulation in Aspergillus fumigatus.";
RL   Mol. Microbiol. 70:27-43(2008).
RN   [9]
RP   FUNCTION.
RX   PubMed=21622789; DOI=10.1128/aem.00182-11;
RA   Blatzer M., Schrettl M., Sarg B., Lindner H.H., Pfaller K., Haas H.;
RT   "SidL, an Aspergillus fumigatus transacetylase involved in biosynthesis of
RT   the siderophores ferricrocin and hydroxyferricrocin.";
RL   Appl. Environ. Microbiol. 77:4959-4966(2011).
RN   [10]
RP   FUNCTION.
RX   PubMed=22106303; DOI=10.1073/pnas.1106399108;
RA   Yasmin S., Alcazar-Fuoli L., Gruendlinger M., Puempel T., Cairns T.,
RA   Blatzer M., Lopez J.F., Grimalt J.O., Bignell E., Haas H.;
RT   "Mevalonate governs interdependency of ergosterol and siderophore
RT   biosyntheses in the fungal pathogen Aspergillus fumigatus.";
RL   Proc. Natl. Acad. Sci. U.S.A. 109:E497-E504(2012).
CC   -!- FUNCTION: Nonribosomal peptide synthase; part of the siderophore
CC       biosynthetic pathway (PubMed:17845073). Aspergillus fumigatus produces
CC       four types of siderophores, low-molecular-mass iron chelators,
CC       including excreted fusarinine C (FsC) and triacetylfusarinine C (TAFC)
CC       for iron uptake and intacellular ferricrocin (FC) for hyphal and
CC       hydroxyferricrocin (HFC) for conidial iron distribution and storage.
CC       TAFC consists of three N(2)-acetyl-N(5)-anhydromevalonyl-N(5)-
CC       hydroxyornithine residues cyclically linked by ester bonds; FC is a
CC       cyclic hexapeptide with the structure Gly-Ser-Gly-(N(5)-acetyl-N(5)-
CC       hydroxyornithine)x3. The biosynthesis of all four siderophores depends
CC       on the hydroxylation of ornithine, catalyzed by the monooxygenase sidA
CC       (PubMed:15504822, PubMed:16113265). Subsequently, the pathways for
CC       biosynthesis of extra- and intracellular siderophores split
CC       (PubMed:17845073). For biosynthesis of extracellular siderophores, the
CC       transacylase sidF transfers anhydromevalonyl to N(5)-hydroxyornithine
CC       (PubMed:17845073). The required anhydromevalonyl-CoA moiety is derived
CC       from mevalonate by CoA ligation and dehydration catalyzed by sidI and
CC       sidH respectively (PubMed:22106303). The acetylation of N(5)-
CC       hydroxyornithine for FC biosynthesis involves the constitutively
CC       expressed sidL (PubMed:21622789). FC is hydroxylated to HFC by an as
CC       yet uncharacterized enzyme during conidiation (PubMed:17845073).
CC       Assembly of fusarinine C (FsC) and FC is catalyzed by two different
CC       nonribosomal peptide synthetases (NRPS), sidD and sidC respectively
CC       (PubMed:17845073). Subsequently, sidG catalyzes N2-acetylation of FsC
CC       for forming TAFC (PubMed:17845073). Both extra- and intracellular
CC       siderophores are crucial for growth during iron limitation and
CC       virulence (PubMed:16113265). {ECO:0000269|PubMed:15504822,
CC       ECO:0000269|PubMed:16113265, ECO:0000269|PubMed:17845073,
CC       ECO:0000269|PubMed:21622789, ECO:0000269|PubMed:22106303}.
CC   -!- PATHWAY: Siderophore biosynthesis. {ECO:0000269|PubMed:17845073}.
CC   -!- INDUCTION: Expression is reduced by up to 90 percent under iron-
CC       depleted conditions. {ECO:0000269|PubMed:15953695}.
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. NRPS3 has the following
CC       architecture: A-T-C-A-T-C. {ECO:0000269|PubMed:15953695,
CC       ECO:0000269|PubMed:17464044}.
CC   -!- SIMILARITY: Belongs to the NRP synthetase family. {ECO:0000305}.
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DR   EMBL; AAHF01000010; EAL86616.2; -; Genomic_DNA.
DR   RefSeq; XP_748654.2; XM_743561.2.
DR   AlphaFoldDB; Q4WF61; -.
DR   SMR; Q4WF61; -.
DR   STRING; 746128.CADAFUBP00004404; -.
DR   EnsemblFungi; EAL86616; EAL86616; AFUA_3G03350.
DR   GeneID; 3506069; -.
DR   KEGG; afm:AFUA_3G03350; -.
DR   VEuPathDB; FungiDB:Afu3g03350; -.
DR   eggNOG; KOG1176; Eukaryota.
DR   eggNOG; KOG1178; Eukaryota.
DR   HOGENOM; CLU_000022_0_12_1; -.
DR   InParanoid; Q4WF61; -.
DR   OMA; LFDFWSH; -.
DR   OrthoDB; 4243at2759; -.
DR   Proteomes; UP000002530; Chromosome 3.
DR   GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
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:0010106; P:cellular response to iron ion starvation; IEP:AspGD.
DR   GO; GO:0019184; P:nonribosomal peptide biosynthetic process; ISM:AspGD.
DR   GO; GO:0019748; P:secondary metabolic process; NAS:AspGD.
DR   GO; GO:0044550; P:secondary metabolite biosynthetic process; IBA: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; IPR025110; AMP-bd_C.
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; 2.
DR   Pfam; PF13193; AMP-binding_C; 1.
DR   Pfam; PF00668; Condensation; 2.
DR   Pfam; PF00550; PP-binding; 2.
DR   SMART; SM00823; PKS_PP; 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; 1.
PE   2: Evidence at transcript level;
KW   Ligase; Phosphopantetheine; Phosphoprotein; Reference proteome; Repeat;
KW   Virulence.
FT   CHAIN           1..2109
FT                   /note="Nonribosomal peptide synthase sidE"
FT                   /id="PRO_0000416544"
FT   DOMAIN          537..613
FT                   /note="Carrier 1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT   DOMAIN          1584..1660
FT                   /note="Carrier 2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT   REGION          31..512
FT                   /note="Adenylation 1"
FT   REGION          646..908
FT                   /note="Condensation 1"
FT   REGION          1058..1555
FT                   /note="Adenylation 2"
FT   REGION          1695..1968
FT                   /note="Condensation 2"
FT   MOD_RES         574
FT                   /note="O-(pantetheine 4'-phosphoryl)serine"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT   MOD_RES         1621
FT                   /note="O-(pantetheine 4'-phosphoryl)serine"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
SQ   SEQUENCE   2109 AA;  233281 MW;  8F19878CD2A8DDBF CRC64;
     MAPVALRDLA ESPELEGTEV VSMKARSSPP LTPPSPPCLV TDYIRHQVES NPDAPAVQCE
     QEQPYSYAAL WQLVEHIAAA GQFRAGRIMP LCMDPSVEFV ATVLAILRAG SAYVILDPEG
     SAQRNRVIAE DCGCEPVIVH EKYAAFFDHS VTIESIQSIQ NHGQLDPPSI TPSDLAYLIY
     TSGSTGTPKG VLLSHRAVSH GIDQFQLNGR KRWLLFYNPI FSAAQRTILA TLSKGACLCL
     TRRDRLATAL PEVLNNLQID ALGITPSALA LLSPGETPAC LQQITTVGEP LSQSLVNKWA
     DRVHLRVSYG LSECAQLNFS RQLQPGDNPR NPGLPSDTTT AIVLEPGTMT RLSVNEPGEL
     CLYGPQVANG YHQRQKETQA AFVKAPKDTH GTMMFRTGDL AVQREDGTFE ILGRIDHQVK
     IHGQRVEPEE VAAKLATVKG VASLACVGCY INERMSLVAA IVPSPEADWG TLVQYLRDHA
     RQSFPPYMVP SYWMSCTEFP TNQNGKVDFR AIRRLAESTE VSKMLGHSTS PKDGATAGLS
     ETASKIAQVW AAVLNLPASS IIPSDSLVAL GGTSIDAIRA IRELKGHGIH VELADMLQAH
     TIEEIADTVQ LDSSPTHVSN EPAAPFDYIS DAVLKADLLA DRRVVDAYPV TALQEGILAS
     TLQGSQDYLY QRVFDVRHLD LVRLQLAFQV VFWRTELLKS TFVAAAKGFL QVVRNDFNLP
     WSEVSLSLSE YLEQDKNNGV TLGEPFMRVA VLDRSILVVS VHHALFDFWS HRFLFDDVAR
     VYYGRRPEKR PEWKSFVGLL HTRDTKASQD FWREHLGEAV PTVLNYAPVT KTSTARRTVS
     QEVRAASSAL RAPLGAIIHA AWALVLSSHI ASKSVTMATA VSGRELPVPG IEALNGPTLA
     VVPYAIAIDS EQTLQQLVQS VNTSLWKVIK HSQVGVRNAL AAAERQGTTL FDTMVNILVN
     GKVNDDISKE VFQLYGRRPV WRTEYTTLNV EEGATGIDVT LTSPMEEHRL EFILEQFCMA
     LNLIASNPRQ TVKATNLVSE TELQFMLQSH KNLPDATRTL NGQFEATVRT YPNRTAINYQ
     NEQFLTYAEL DSEANRMTHY LSELGVVPGD IVPLLLEKSP LMIKAILALF KLGAAYVPLS
     PENPLERNAY IARDVSAKFV LTEKEHEAYF ASESDIPSVL LDQANLSQYG PEPQLVTVSP
     DALAYLLYTS GSTGLPKGVM VTHGACAAAM QSIIEFEHRQ GQESRMLQFS NYVFDVSLYD
     FFVALHSGGT LCIAPSERLL NNLAEVINEM NVNHVFLTPT VARLLNPKDV PNLESMTVGG
     EQLTRDVVTT WASRVTLRNG YGPTEASVLV TMKDVDTDTT GGNIGRPLAS VGAIVLEADG
     VRPVPYGAVG ELCFFGPQLA QGYFKKPDIT SAAFIESEVL NGRRLYRSGD LARYLPNGDI
     ECLGRKDDQV KINGHRIELG EIEQAFLRTG EIKDCVLTVW KHNSTAHLVA VAVFDGASSE
     KPGEVLPLDG FAENVQRVRS KLTGLTPYMI PKAIVPLSSL PRLPSGKANR KQLKAMVQSL
     SQGELTKFSF DKVGAAQSKG AVIPLASETQ KVLQQGWIET LQLADDDFGL EADFLSLGGD
     SIAAINLVSW LRRKQLKISV RDVLKYTSLG AMADQLKGES GDAHQIQKKT FTPPSEIDAA
     ISAAGLQATE YEYIYPCPPG QAEFLTQGAH PEALWSLMTV RKVGSDFAPR QWIDLVRQLT
     TTNEILRTTF TRCHGNWYGV VLRDATPVVE IYEDVSNEQR QQIIKSLDDY RFVFGKPFIR
     YAILHLSTGE TEIVTKLDHG LYDGTLLRIF GEHFQAYQDN VPVDRFTSFK DFAFHIWQMD
     KSRTLSFWKQ SEKRPIAFEF PSSSGTEPRI NSVHVHTINL EFDAFAKSTG ATVSIIFQSI
     FQLWLALRSN QRDVAFDYLY TGRNIDLPDP QTINGTCANF LPMRSKVDPS MPVSEFLRQT
     QDEFWQYTEN STVGMDEIHE ACETTREGFS NKTLFLFQPF EPAPATAKQY EKWIVMAKSQ
     VTMPQPYAVV FEVVKTADVN EYKLKFAFDK RVYEKEQVQG EAQVIEKLLA KVMENAEASV
     GDVLGSFRS