IVOA_EMENI
ID IVOA_EMENI Reviewed; 1704 AA.
AC C8V7P4; Q5B489;
DT 23-MAY-2018, integrated into UniProtKB/Swiss-Prot.
DT 03-NOV-2009, sequence version 1.
DT 25-MAY-2022, entry version 69.
DE RecName: Full=Nonribosomal peptide synthetase ivoA {ECO:0000303|PubMed:28108400};
DE Short=NRPS ivoA {ECO:0000303|PubMed:28108400};
DE EC=5.1.-.- {ECO:0000269|PubMed:31573806};
DE AltName: Full=Ivory mutation-related protein A {ECO:0000303|Ref.3};
GN Name=ivoA {ECO:0000303|PubMed:28108400}; ORFNames=AN4641, ANIA_10576;
OS Emericella nidulans (strain FGSC A4 / ATCC 38163 / CBS 112.46 / NRRL 194 /
OS M139) (Aspergillus nidulans).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Aspergillaceae; Aspergillus;
OC Aspergillus subgen. Nidulantes.
OX NCBI_TaxID=227321;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=FGSC A4 / ATCC 38163 / CBS 112.46 / NRRL 194 / M139;
RX PubMed=16372000; DOI=10.1038/nature04341;
RA Galagan J.E., Calvo S.E., Cuomo C., Ma L.-J., Wortman J.R., Batzoglou S.,
RA Lee S.-I., Bastuerkmen M., Spevak C.C., Clutterbuck J., Kapitonov V.,
RA Jurka J., Scazzocchio C., Farman M.L., Butler J., Purcell S., Harris S.,
RA Braus G.H., Draht O., Busch S., D'Enfert C., Bouchier C., Goldman G.H.,
RA Bell-Pedersen D., Griffiths-Jones S., Doonan J.H., Yu J., Vienken K.,
RA Pain A., Freitag M., Selker E.U., Archer D.B., Penalva M.A., Oakley B.R.,
RA Momany M., Tanaka T., Kumagai T., Asai K., Machida M., Nierman W.C.,
RA Denning D.W., Caddick M.X., Hynes M., Paoletti M., Fischer R., Miller B.L.,
RA Dyer P.S., Sachs M.S., Osmani S.A., Birren B.W.;
RT "Sequencing of Aspergillus nidulans and comparative analysis with A.
RT fumigatus and A. oryzae.";
RL Nature 438:1105-1115(2005).
RN [2]
RP GENOME REANNOTATION.
RC STRAIN=FGSC A4 / ATCC 38163 / CBS 112.46 / NRRL 194 / M139;
RX PubMed=19146970; DOI=10.1016/j.fgb.2008.12.003;
RA Wortman J.R., Gilsenan J.M., Joardar V., Deegan J., Clutterbuck J.,
RA Andersen M.R., Archer D., Bencina M., Braus G., Coutinho P., von Dohren H.,
RA Doonan J., Driessen A.J., Durek P., Espeso E., Fekete E., Flipphi M.,
RA Estrada C.G., Geysens S., Goldman G., de Groot P.W., Hansen K.,
RA Harris S.D., Heinekamp T., Helmstaedt K., Henrissat B., Hofmann G.,
RA Homan T., Horio T., Horiuchi H., James S., Jones M., Karaffa L.,
RA Karanyi Z., Kato M., Keller N., Kelly D.E., Kiel J.A., Kim J.M.,
RA van der Klei I.J., Klis F.M., Kovalchuk A., Krasevec N., Kubicek C.P.,
RA Liu B., Maccabe A., Meyer V., Mirabito P., Miskei M., Mos M., Mullins J.,
RA Nelson D.R., Nielsen J., Oakley B.R., Osmani S.A., Pakula T., Paszewski A.,
RA Paulsen I., Pilsyk S., Pocsi I., Punt P.J., Ram A.F., Ren Q., Robellet X.,
RA Robson G., Seiboth B., van Solingen P., Specht T., Sun J.,
RA Taheri-Talesh N., Takeshita N., Ussery D., vanKuyk P.A., Visser H.,
RA van de Vondervoort P.J., de Vries R.P., Walton J., Xiang X., Xiong Y.,
RA Zeng A.P., Brandt B.W., Cornell M.J., van den Hondel C.A., Visser J.,
RA Oliver S.G., Turner G.;
RT "The 2008 update of the Aspergillus nidulans genome annotation: a community
RT effort.";
RL Fungal Genet. Biol. 46:S2-13(2009).
RN [3]
RP FUNCTION, DISRUPTION PHENOTYPE, AND PATHWAY.
RX DOI=10.1016/0031-9422(83)85048-1;
RA McCorkindale N.J., Hayes D., Johnston G.A., Clutterbuck A.J.;
RT "N-acetyl-6-hydroxytryptophan a natural substrate of a monophenol oxidase
RT from Aspergillus nidulans.";
RL Phytochemistry 22:1026-1028(1983).
RN [4]
RP FUNCTION, DISRUPTION PHENOTYPE, AND PATHWAY.
RX PubMed=2126551; DOI=10.1099/00221287-136-9-1725;
RA Birse C.E., Clutterbuck A.J.;
RT "N-acetyl-6-hydroxytryptophan oxidase, a developmentally controlled phenol
RT oxidase from Aspergillus nidulans.";
RL J. Gen. Microbiol. 136:1725-1730(1990).
RN [5]
RP IDENTIFICATION OF THE IVO CLUSTER.
RX PubMed=23617571; DOI=10.1186/1471-2180-13-91;
RA Inglis D.O., Binkley J., Skrzypek M.S., Arnaud M.B., Cerqueira G.C.,
RA Shah P., Wymore F., Wortman J.R., Sherlock G.;
RT "Comprehensive annotation of secondary metabolite biosynthetic genes and
RT gene clusters of Aspergillus nidulans, A. fumigatus, A. niger and A.
RT oryzae.";
RL BMC Microbiol. 13:91-91(2013).
RN [6]
RP FUNCTION, AND PATHWAY.
RX PubMed=28108400; DOI=10.1016/j.fgb.2017.01.006;
RA Sung C.T., Chang S.L., Entwistle R., Ahn G., Lin T.S., Petrova V.,
RA Yeh H.H., Praseuth M.B., Chiang Y.M., Oakley B.R., Wang C.C.C.;
RT "Overexpression of a three-gene conidial pigment biosynthetic pathway in
RT Aspergillus nidulans reveals the first NRPS known to acetylate
RT tryptophan.";
RL Fungal Genet. Biol. 101:1-6(2017).
RN [7]
RP FUNCTION, DOMAIN, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND
RP MUTAGENESIS OF SER-785; HIS-963 AND HIS-1428.
RX PubMed=31573806; DOI=10.1021/jacs.9b08898;
RA Hai Y., Jenner M., Tang Y.;
RT "Complete stereoinversion of L-tryptophan by a fungal single-module
RT nonribosomal peptide synthetase.";
RL J. Am. Chem. Soc. 141:16222-16226(2019).
CC -!- FUNCTION: Nonribosomal peptide synthetase; part of the pathway that
CC mediates the biosynthesis of the gray-brown conidiophore pigment
CC (PubMed:23617571, PubMed:28108400). The first step of the pathway is
CC performed by the nonribosomal peptide synthetase ivoA that catalyzes
CC ATP-dependent unidirectional stereoinversion of L-tryptophan to D-
CC tryptophan with complete conversion (PubMed:31573806). While the
CC stereoinversion is catalyzed by the epimerization (E) domain of ivoA,
CC the terminal condensation (C) domain stereoselectively hydrolyzes D-
CC tryptophanyl-S-phosphopantetheine thioester and thus represents a non-
CC canonical C domain function (PubMed:31573806). D-tryptophan is
CC acetylated, probably by an endogenous acetyltransferase (Probable). N-
CC acetyltryptophan is further 6-hydroxylated into N-acetyl-6-
CC hydroxytryptophan (AHT) by the cytochrome P450 monooxygenase ivoC
CC (PubMed:28108400). N-acetyl-6-hydroxytryptophan is substrate of the N-
CC acetyl-6-hydroxytryptophan oxidase ivoB to produce the gray-brown
CC conidiophore pigment (PubMed:2126551, PubMed:28108400, Ref.3).
CC {ECO:0000269|PubMed:2126551, ECO:0000269|PubMed:23617571,
CC ECO:0000269|PubMed:28108400, ECO:0000269|PubMed:31573806,
CC ECO:0000269|Ref.3, ECO:0000305|PubMed:31573806}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + H2O + L-tryptophan = AMP + D-tryptophan + diphosphate +
CC H(+); Xref=Rhea:RHEA:63892, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:33019, ChEBI:CHEBI:57719,
CC ChEBI:CHEBI:57912, ChEBI:CHEBI:456215;
CC Evidence={ECO:0000269|PubMed:31573806};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:63893;
CC Evidence={ECO:0000269|PubMed:31573806};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=50 uM for L-tryptophan {ECO:0000269|PubMed:31573806};
CC -!- PATHWAY: Pigment biosynthesis. {ECO:0000269|PubMed:2126551,
CC ECO:0000269|PubMed:28108400, ECO:0000269|Ref.3}.
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 are
CC present within the NRP synthetase. IvoA has the following mono-modular
CC architecture: A-T-E-C. {ECO:0000305|PubMed:28108400,
CC ECO:0000305|PubMed:31573806}.
CC -!- DISRUPTION PHENOTYPE: Impairs the production of the gray-brown
CC conidiophore pigment and leads to 'ivory' (colorless) conidiophores
CC (PubMed:2126551). {ECO:0000269|PubMed:2126551}.
CC -!- SIMILARITY: Belongs to the NRP synthetase family. {ECO:0000305}.
CC -!- CAUTION: Genetic studies provided compelling evidence implicating ivoA
CC in the biosynthesis of N-acetyl-hydroxytryptophan (Ref.3,
CC PubMed:28108400). The proposed acetyltransferase activity of ivoA is
CC however an unlikely fit for a single-module NRPS and further studies
CC showed that ivoA actually catalyzes ATP-dependent unidirectional
CC stereo-inversion of L-tryptophan to D-tryptophan (PubMed:31573806).
CC {ECO:0000269|PubMed:28108400, ECO:0000269|PubMed:31573806,
CC ECO:0000269|Ref.3}.
CC -!- SEQUENCE CAUTION:
CC Sequence=EAA60443.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
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DR EMBL; BN001303; CBF77087.1; -; Genomic_DNA.
DR EMBL; AACD01000079; EAA60443.1; ALT_SEQ; Genomic_DNA.
DR RefSeq; XP_662245.1; XM_657153.1.
DR AlphaFoldDB; C8V7P4; -.
DR SMR; C8V7P4; -.
DR STRING; 162425.CADANIAP00005791; -.
DR EnsemblFungi; CBF77087; CBF77087; ANIA_10576.
DR EnsemblFungi; EAA60443; EAA60443; AN4641.2.
DR GeneID; 2872441; -.
DR KEGG; ani:AN4641.2; -.
DR VEuPathDB; FungiDB:AN10576; -.
DR eggNOG; KOG1178; Eukaryota.
DR HOGENOM; CLU_000022_60_2_1; -.
DR InParanoid; C8V7P4; -.
DR OMA; DHAPDSK; -.
DR OrthoDB; 4243at2759; -.
DR Proteomes; UP000000560; Chromosome III.
DR Proteomes; UP000005890; Unassembled WGS sequence.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0009277; C:fungal-type cell wall; IDA:AspGD.
DR GO; GO:0016853; F:isomerase 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:0048315; P:conidium formation; IMP:AspGD.
DR GO; GO:0046148; P:pigment biosynthetic process; IMP:AspGD.
DR GO; GO:0075307; P:positive regulation of conidium formation; IMP: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; -; 1.
DR Gene3D; 3.30.300.30; -; 1.
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; IPR009081; PP-bd_ACP.
DR Pfam; PF00501; AMP-binding; 1.
DR Pfam; PF00668; Condensation; 2.
DR Pfam; PF00550; PP-binding; 1.
DR SUPFAM; SSF47336; SSF47336; 1.
DR TIGRFAMs; TIGR01733; AA-adenyl-dom; 1.
DR PROSITE; PS00455; AMP_BINDING; 1.
DR PROSITE; PS50075; CARRIER; 1.
PE 1: Evidence at protein level;
KW Isomerase; Phosphopantetheine; Phosphoprotein; Reference proteome.
FT CHAIN 1..1704
FT /note="Nonribosomal peptide synthetase ivoA"
FT /id="PRO_0000444120"
FT DOMAIN 748..827
FT /note="Carrier"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258,
FT ECO:0000305|PubMed:28108400, ECO:0000305|PubMed:31573806"
FT REGION 234..620
FT /note="Adenylation"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:28108400,
FT ECO:0000305|PubMed:31573806"
FT REGION 840..1266
FT /note="Epimerization (E) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:31573806"
FT REGION 1325..1477
FT /note="Condensation"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:28108400,
FT ECO:0000305|PubMed:31573806"
FT MOD_RES 785
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT MUTAGEN 785
FT /note="S->A: Inactivates the T domain by completely
FT abolishing the incorporation of L-tryptophan."
FT /evidence="ECO:0000269|PubMed:31573806"
FT MUTAGEN 963
FT /note="H->A: Compromises the catalytic activity, but does
FT not affect substrate binding at the A domain."
FT /evidence="ECO:0000269|PubMed:31573806"
FT MUTAGEN 1428
FT /note="H->A: Compromises the catalytic activity, but does
FT not affect substrate binding at the A domain."
FT /evidence="ECO:0000269|PubMed:31573806"
SQ SEQUENCE 1704 AA; 188956 MW; 0BEA54515293E0D2 CRC64;
MASPIIQPAG AGIHDIFTQL ELWESIDKGL SMITILRDND VLWKPFLQLT LFNQLNIVRK
AWSATIQKAS ESDKVPTLKD VYTSESSFIA QALLDTKNLQ ITPPATPRTA LSGALLAKTI
VIFHHSERAQ EELGTELPEE VRSLVNQNAI CLKVLYNANQ WHIDLHYKRD SLSSAQAGEV
AEIFEQYLEE ALEAVASAIP PSPPVEDDNA GHGGLCKERT DCPKVNRCIH DLIEEQAIAR
PDQEGICAYD GSLSYAGLSK LSSVLAEQLK TFGARPEQRV AILMNKSFWY PVVVLAVLKS
GAAFVPLDPS HPKNRLKQLI SEIEPCALIT TSVLSELADD LGCPSLAIDS DLTRSKEGST
TALLPNTSAS PNNAAYIIFT SGSTGKPKGV VVEHSALSTS AITRGVVLGL GPDSRVLQYA
PHTFDVSVDE ILTTLIHGGC VCVPSEDDRF SIAHFMESAR VTVALLTPTS ARTLHPDEVP
SLRILQTGGE VLTEDVNDKW SNRVTLFNVY GPTEASVACV ISNRTGLKGA GHVLGQAVGG
KLWIVDPDDI ERHLPDNEVG ELVISGAILA RGYFRDPSRT ESSFVRMRNG ERVYRTGDLA
SMDSAGTIIY HGRKDLEVKI RGQRINIAEI EIAILQCDLV HSVVVEYPRS GLFEKKLVAV
LRFEDSSSDA EDGLFGGAKG LTEDIYCLLL SHVSSVLTPA MIPSKWLSLP CVPQMPSGKA
DRKQVRGWLE DMDKRTYTRI FHPNGTDNLI SDPSDSMVAI WLKVLKLEPQ SLRLDQSFIR
NGGDSIMAME ARHQAHEAGI NIDVRELLGS RALQEIGEMA TKTSAVEEVS KIEDDRDEPF
PLSPVQQMYF DKVSDPSLGL QQRVCVEIMT KIQPDMLREA LNHVIQKHRM LAARFTKHMG
QWMQQVPFGK NLKHLSRCHI YSQAVGSLGD FCSEPMALED GTLLHAHLQS SGERQTLVLC
VHHLVVDFVS WRVILQDLHD ALAAAQNGLP SGISRSTLTF QQWCREQTKY ASTLIPEAVL
PFAPGPVNLR FWQPSNVQAV SNTYSEIVQH DFRLSSTQTT QMLEKFTTAT VHPTDLMLAT
FALAFKRIFT ERDTPTIFIE GHGREPWHAS LDVSQTVGWF TAAFPIHLPK DTLLNTTTAI
LGASERRRSV LANGHPYWAC RYLSPNGQKV FGDDPRHQEM EFVFNYAGSI VQRAPGQTLF
AENVRIAEIG HPNCERFSLF DIGAAIEMPS SELVVSFTFP KGIAHRERVA ELVKTYQELL
ETAVERDLDL SAKLSSPLVC PADVVRSLEV NGVCIERDVE IVYTPSSIQQ HMLWRQSQEP
WFYRVQGDWT IEKTTTQSEP VDIDRLSHAW NQVVHRHTTL RTVFRYSSEE ERFVAIVLHE
VKPAISIIRK GIQTSGSLCR DDDLSPPHRM VLREKDNGSV VCELEFSHTI IDAASRSIVV
QDLLDAYDGK LAHRPLDFPP FWEYIRLAQS STPSARKEEL HRAGRVVTLP FQPTHVLSKV
PEACKKNEIT ISSFFMTAWS IVLAKHFVAH NQRVDSTSSQ AVAFDYVLSD RSANIPGIES
AVGPYIRLPT LETHVKEGVS LKNIARGLHA QCTFQSLSQS TQDGSSLELP SKATALQKYS
TLVNIRNSGS DSLDLVSDSG EWKWILQGFS DPWDYDLVFA VNVHAGKVTG WTVEYADGVV
EHSAADEIAK DLNDVVERMV CEII
