SIDD_ASPFU
ID SIDD_ASPFU Reviewed; 2083 AA.
AC Q4WF53;
DT 18-APR-2012, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2005, sequence version 1.
DT 25-MAY-2022, entry version 96.
DE RecName: Full=Nonribosomal peptide synthase sidD {ECO:0000303|PubMed:15953695};
DE Short=NPRS sidD {ECO:0000303|PubMed:15953695};
DE EC=6.3.2.- {ECO:0000305|PubMed:17845073};
DE AltName: Full=Siderophore synthetase D {ECO:0000303|PubMed:17464044};
GN Name=NRPS4 {ECO:0000303|PubMed:16962256};
GN Synonyms=sidD {ECO:0000303|PubMed:15953695}; ORFNames=AFUA_3G03420;
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 FUNCTION, DISRUPTION PHENOTYPE, AND INDUCTION.
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 [7]
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 [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:15953695, PubMed:17845073,
CC PubMed:17464044). Aspergillus fumigatus produces four types of
CC siderophores, low-molecular-mass iron chelators, including excreted
CC fusarinine C (FsC) and triacetylfusarinine C (TAFC) for iron uptake;
CC and intacellular ferricrocin (FC) for hyphal and hydroxyferricrocin
CC (HFC) for conidial iron distribution and storage. TAFC consists of
CC three N(2)-acetyl-N(5)-anhydromevalonyl-N(5)-hydroxyornithine residues
CC cyclically linked by ester bonds; FC is a cyclic hexapeptide with the
CC structure Gly-Ser-Gly-(N(5)-acetyl-N(5)-hydroxyornithine)x3. The
CC biosynthesis of all four siderophores depends on the hydroxylation of
CC ornithine, catalyzed by the monooxygenase sidA (PubMed:15504822,
CC PubMed:16113265). Subsequently, the pathways for biosynthesis of
CC extra- and intracellular siderophores split (PubMed:17845073). For
CC biosynthesis of extracellular siderophores, the transacylase sidF
CC transfers anhydromevalonyl to N(5)-hydroxyornithine (PubMed:17845073).
CC The required anhydromevalonyl-CoA moiety is derived from mevalonate by
CC CoA ligation and dehydration catalyzed by sidI and sidH respectively
CC (PubMed:22106303). The acetylation of N(5)-hydroxyornithine for FC
CC biosynthesis involves the constitutively expressed sidL
CC (PubMed:21622789). FC is hydroxylated to HFC by an as yet
CC uncharacterized enzyme during conidiation (PubMed:17845073). Assembly
CC of fusarinine C (FsC) and FC is catalyzed by two different nonribosomal
CC peptide synthetases (NRPS), sidD and sidC respectively
CC (PubMed:15953695, PubMed:17845073, PubMed:17464044). Subsequently, sidG
CC catalyzes N2-acetylation of FsC for forming TAFC (PubMed:17845073).
CC Both extra- and intracellular siderophores are crucial for growth
CC during iron limitation and virulence (PubMed:16113265).
CC {ECO:0000269|PubMed:15504822, ECO:0000269|PubMed:15953695,
CC ECO:0000269|PubMed:16113265, ECO:0000269|PubMed:17464044,
CC ECO:0000269|PubMed:17845073, ECO:0000269|PubMed:21622789,
CC ECO:0000269|PubMed:22106303}.
CC -!- PATHWAY: Siderophore biosynthesis. {ECO:0000269|PubMed:17845073}.
CC -!- INDUCTION: Expression is induced during iron starvation
CC (PubMed:15953695, PubMed:17845073). {ECO:0000269|PubMed:15953695,
CC ECO:0000269|PubMed:17845073}.
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. NRPS4 has the following
CC architecture: A-T-C-A-C. {ECO:0000269|PubMed:15953695,
CC ECO:0000269|PubMed:17464044}.
CC -!- DISRUPTION PHENOTYPE: Prevents synthesis of TAFC and FsC without
CC affecting FC production (PubMed:17845073).
CC {ECO:0000269|PubMed:17845073}.
CC -!- SIMILARITY: Belongs to the NRP synthetase family. {ECO:0000305}.
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DR EMBL; AAHF01000010; EAL86624.1; -; Genomic_DNA.
DR RefSeq; XP_748662.1; XM_743569.1.
DR AlphaFoldDB; Q4WF53; -.
DR SMR; Q4WF53; -.
DR STRING; 746128.CADAFUBP00004398; -.
DR PRIDE; Q4WF53; -.
DR EnsemblFungi; EAL86624; EAL86624; AFUA_3G03420.
DR GeneID; 3506154; -.
DR KEGG; afm:AFUA_3G03420; -.
DR VEuPathDB; FungiDB:Afu3g03420; -.
DR eggNOG; KOG1178; Eukaryota.
DR HOGENOM; CLU_000022_60_2_1; -.
DR InParanoid; Q4WF53; -.
DR OMA; FNPYPLM; -.
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:0006696; P:ergosterol biosynthetic process; IMP:AspGD.
DR GO; GO:1900551; P:N',N'',N'''-triacetylfusarinine C biosynthetic process; IMP: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; IMP:AspGD.
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; -; 1.
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; IPR020806; PKS_PP-bd.
DR InterPro; IPR009081; PP-bd_ACP.
DR Pfam; PF00501; AMP-binding; 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; 1.
DR PROSITE; PS50075; CARRIER; 2.
PE 2: Evidence at transcript level;
KW Ligase; Phosphopantetheine; Phosphoprotein; Reference proteome; Repeat;
KW Virulence.
FT CHAIN 1..2083
FT /note="Nonribosomal peptide synthase sidD"
FT /id="PRO_0000416545"
FT DOMAIN 764..840
FT /note="Carrier 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT DOMAIN 1557..1633
FT /note="Carrier 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT REGION 251..650
FT /note="Adenylation 1"
FT REGION 876..1146
FT /note="Condensation 1"
FT REGION 1336..1421
FT /note="Adenylation 2"
FT REGION 1674..1946
FT /note="Condensation 2"
FT MOD_RES 801
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT MOD_RES 1594
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
SQ SEQUENCE 2083 AA; 228752 MW; 977306F5EA529610 CRC64;
MGSIQQDDVH NQIDHCNQSD DLPAARLNCN DVELFEVAGL ACDETSSPTG MRDEMVLLSW
LIALLRTREG GQIRYEWAYR YPEEEPVPRC LAMNEVVAGL QSSVKETAAA VSRHISADVS
SPPAPASLLL STSSLSQTSD EAKDEGLLHL EIAFENGLCK IRPTWHSENM LPFTVTRYAR
TLIDTVRLCI SNCDAAIQDC LRPTAYDLDE IWRWNHNLPP TYNFCMHEII SDQAQKFPDK
EAIASWDGSL TYRQIDQYSS FVARSLIGMG VGLHDVLPVC FEKSRWTIVA VLAVMKAGAT
FVLMDPTLPL ARLQNMAQQV GAKMMVSSRG QYNLATEIIP NANVLVVEEN TFSSLSAEQN
GEPLPTVPSS ALMYMIFTSG STGTPKGVKI SHETYTSSAI PRANAVGYTE DSRVLDFASY
AFDVSIDSML LTLGNGGCLC IPSDEDRLND INGVIRRMKV NYAGLTPSVA RILDADVISS
LSGLGLGGEA VSARDVNLWG QDTRIIIGYG PCECTIGCTV NSSAATGRDY ISIGPGNGAV
IWIVDPNDHE SLVPLGAVGE LLVEGPIVGQ GYLNDPEKTA AAFIEDPSWL VAGHEGYPGR
RGRLYKTGDL GRYDPDGSGG IVFVGRKDTQ VKLRGQRVEL GEIESQLRAR LPSETTVIAE
VIVPQGSGGQ PTLVAFVAAQ TTKGHDHTGL EAAELPDELR RALSEADAEL AKVLPRYMVP
TAYIPVNHIP TLISGKTDRK RLRQFGATVD LRQLDQDATN TAARELSDLE RRLRQAWSQT
LKLQACSIRL QDNFFALGGD SLTAMKLVSV CRSQGLDLSV TSMFSNPTLS AMASVVRICD
VDVQRTVPAF SMITSDMNSA CVEAAEPCGV GPADIEDIYP CTPTQESLFT FSLKSVKPYV
AQRVLCIPSH IDLNAWRKAW EDVVAALPIL RTRVAQLQEP GLQQVVLKNS ISWTQASDLA
EYLENDRTQK MNLGESLARY AIVEDSADGK RYMVWTIHHV LYDGWSEPII LKQVSDALQG
QPVEVKAQMR DFVRFVRDSD DAAVQEFWRR ELKGAVGPQF PRLPSRDFMP TPDALVERQV
SLDTSSGSPF TMATLIRGAW ALVASQYTGS DDIVFGETLT GRDIPLPGVE SIVGPLIATV
PIRVRILRGS TVESYLQAVQ QSVLARTPYQ HLGMQNIRKV SQDAQHACET GTGLVIQPEP
EYVGSELGVE RGDVVLEALH FNPYPLMLAC GIRKGGFRVC ASFDSSLIET RQMERMLAQL
ETACWQLSQG LSRKVDEISC LPEAELNQIW QWNRSPPLSL DETTSRLRAN ASTKPGSSYP
PAVVPWVCSP RNSSLLSPIG CVGELWLEGA LLSGDTVDSP AWLVAGSSTC AGRTGKVQAT
GDMVQLREDG SLVFVGRKEN VVPVQGHAVD ITEIERHLAE HLPPTIRAAA TVVRSSSDQE
LVMFIEQPAA EEACIELLSE KREIVCDAPD KAFQTTICAT IPGSLAAVLK KLDKYMRDSL
PSYMAPSAYI VVEKLPNTMD DIDHNLLNQI ASQVTPQILN ELRDGLSNAW TKATAPNHLS
ASESILRSAW AKVLRVDPEQ IDVDDNFFRR GGDSVLAMKL VSSLRAQGYS LSVADIFRHM
RLSDAARVMK VDERSTEKIN SYQPFSMLRL PDVQQFLANI VRPQLGDQHW PIRDVLPVTD
SQDMDIRATI QPPRTSIQYT MLYFDNSVDR ERLFRSCSDL VKTHEILRTV FISHESSFLQ
VVLNELEIPV RAHKTDKQLD QYVASLFRED IESNFQLGCP FLRLFYVEGN NGESCLVIGL
SHAQYDGVSL PRLLQDLDAL YTGTQLATFS PFSLYMAQTS EEAIQNKAAA YWRNLLSSSS
LSTLDGPSSD PTDKAIFHTR PVNIHPLKEI TTANLLTAAW AMVLARRLQT PDVTFGSVTS
GRTLDIPNAE NFMGPCYQLT PVRVPFHPDW TASDLLNFVQ TQSAESAAHD FLGFEKIAKL
AGWASGRQGF DSIVHHQDWE DFDMMPFGGG SCRVDIANPH GDAAYPVKAV SFVKEGEIHV
GVVCSERDVM FVDEVLGELA AAVVELAGQS TEVLLDSKLF SGQ
