MELA_ASPTN
ID MELA_ASPTN Reviewed; 925 AA.
AC Q0CRX1; A0A2I6SS15;
DT 11-DEC-2019, integrated into UniProtKB/Swiss-Prot.
DT 11-DEC-2019, sequence version 2.
DT 03-AUG-2022, entry version 78.
DE RecName: Full=Aspulvinone E synthetase melA {ECO:0000303|PubMed:27133313};
DE EC=2.3.1.- {ECO:0000269|PubMed:27133313, ECO:0000269|PubMed:29270299, ECO:0000269|PubMed:29305695};
DE AltName: Full=Nonribosomal peptide synthase melA {ECO:0000303|PubMed:27133313};
GN Name=melA {ECO:0000303|PubMed:23841722}; ORFNames=ATEG_03563;
OS Aspergillus terreus (strain NIH 2624 / FGSC A1156).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Aspergillaceae; Aspergillus;
OC Aspergillus subgen. Circumdati.
OX NCBI_TaxID=341663;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], DOMAIN, FUNCTION, AND CATALYTIC ACTIVITY.
RC STRAIN=NIH 2624 / FGSC A1156;
RX PubMed=29305695; DOI=10.1007/s00253-017-8719-1;
RA Huehner E., Backhaus K., Kraut R., Li S.M.;
RT "Production of alpha-keto carboxylic acid dimers in yeast by overexpression
RT of NRPS-like genes from Aspergillus terreus.";
RL Appl. Microbiol. Biotechnol. 102:1663-1672(2018).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=NIH 2624 / FGSC A1156;
RA Birren B.W., Lander E.S., Galagan J.E., Nusbaum C., Devon K., Henn M.,
RA Ma L.-J., Jaffe D.B., Butler J., Alvarez P., Gnerre S., Grabherr M.,
RA Kleber M., Mauceli E.W., Brockman W., Rounsley S., Young S.K., LaButti K.,
RA Pushparaj V., DeCaprio D., Crawford M., Koehrsen M., Engels R.,
RA Montgomery P., Pearson M., Howarth C., Larson L., Luoma S., White J.,
RA Alvarado L., Kodira C.D., Zeng Q., Oleary S., Yandava C., Denning D.W.,
RA Nierman W.C., Milne T., Madden K.;
RT "Annotation of the Aspergillus terreus NIH2624 genome.";
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=23841722; DOI=10.1021/ol401384v;
RA Guo C.J., Knox B.P., Sanchez J.F., Chiang Y.M., Bruno K.S., Wang C.C.;
RT "Application of an efficient gene targeting system linking secondary
RT metabolites to their biosynthetic genes in Aspergillus terreus.";
RL Org. Lett. 15:3562-3565(2013).
RN [4]
RP INDUCTION, DOMAIN, DISRUPTION PHENOTYPE, FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=27133313; DOI=10.1016/j.chembiol.2016.03.014;
RA Geib E., Gressler M., Viediernikova I., Hillmann F., Jacobsen I.D.,
RA Nietzsche S., Hertweck C., Brock M.;
RT "A non-canonical melanin biosynthesis pathway protects Aspergillus terreus
RT conidia from environmental stress.";
RL Cell Chem. Biol. 23:587-597(2016).
RN [5]
RP FUNCTION, CATALYTIC ACTIVITY, AND SUBCELLULAR LOCATION.
RX PubMed=29270299; DOI=10.1186/s40694-017-0042-1;
RA Geib E., Brock M.;
RT "ATNT: an enhanced system for expression of polycistronic secondary
RT metabolite gene clusters in Aspergillus niger.";
RL Fungal Biol. Biotechnol. 4:13-13(2017).
CC -!- FUNCTION: Nonribosomal peptide synthase; part of the gene cluster that
CC mediates the biosynthesis of Asp-melanin, a pigment that confers
CC resistance against UV light and hampers phagocytosis by soil amoeba
CC (PubMed:29305695, PubMed:23841722, PubMed:27133313, PubMed:29270299).
CC The nonribosomal peptide synthase melA converts 4-hydroxyphenylpyruvate
CC (4-HPPA) to aspulvinone E (PubMed:29305695, PubMed:27133313,
CC PubMed:29270299). The tyrosinase tyrP then performs hydroxylations of
CC both aromatic moieties of aspulvinone E (PubMed:27133313,
CC PubMed:29305695). The product of tyrP is highly unstable, and, due to
CC the high reactivity of methides and ortho-diquinones, the polymeric
CC Asp-melanin forms spontaneously (PubMed:27133313).
CC {ECO:0000269|PubMed:23841722, ECO:0000269|PubMed:27133313,
CC ECO:0000269|PubMed:29270299, ECO:0000269|PubMed:29305695}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2 3-(4-hydroxyphenyl)pyruvate = aspulvinone E + H2O;
CC Xref=Rhea:RHEA:63824, ChEBI:CHEBI:15377, ChEBI:CHEBI:36242,
CC ChEBI:CHEBI:58240; Evidence={ECO:0000269|PubMed:27133313,
CC ECO:0000269|PubMed:29270299, ECO:0000269|PubMed:29305695};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:63825;
CC Evidence={ECO:0000269|PubMed:27133313, ECO:0000269|PubMed:29270299,
CC ECO:0000269|PubMed:29305695};
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:29270299}.
CC -!- INDUCTION: Expression is induced during conidiation.
CC {ECO:0000269|PubMed:27133313}.
CC -!- DOMAIN: AtrA has a A-T-TE domain architecture (Probable). The
CC adenylation (A) domain recognizes and activates the aryl acid
CC substrates, and loads them onto the thiolation (T) domain (Probable).
CC The thioesterase (TE) domain shares the missing condensation (C) domain
CC function, and is responsible for condensation and final product release
CC (Probable). {ECO:0000305|PubMed:27133313, ECO:0000305|PubMed:29305695}.
CC -!- DISRUPTION PHENOTYPE: Results in white conidia.
CC {ECO:0000269|PubMed:23841722, ECO:0000269|PubMed:27133313}.
CC -!- SIMILARITY: Belongs to the NRP synthetase family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=EAU36837.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
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DR EMBL; MG384313; AUO29223.1; -; mRNA.
DR EMBL; CH476597; EAU36837.1; ALT_SEQ; Genomic_DNA.
DR RefSeq; XP_001212741.1; XM_001212741.1.
DR AlphaFoldDB; Q0CRX1; -.
DR SMR; Q0CRX1; -.
DR EnsemblFungi; EAU36837; EAU36837; ATEG_03563.
DR GeneID; 4317932; -.
DR eggNOG; KOG1176; Eukaryota.
DR HOGENOM; CLU_000022_23_6_1; -.
DR OrthoDB; 127131at2759; -.
DR Proteomes; UP000007963; Unassembled WGS sequence.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0031177; F:phosphopantetheine binding; IEA:InterPro.
DR GO; GO:0016740; F:transferase activity; IEA:UniProtKB-KW.
DR GO; GO:0044249; P:cellular biosynthetic process; IEA:UniProt.
DR Gene3D; 1.10.1200.10; -; 1.
DR Gene3D; 3.30.300.30; -; 1.
DR Gene3D; 3.40.50.12780; -; 1.
DR Gene3D; 3.40.50.1820; -; 1.
DR InterPro; IPR029058; AB_hydrolase.
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; IPR020806; PKS_PP-bd.
DR InterPro; IPR009081; PP-bd_ACP.
DR InterPro; IPR001031; Thioesterase.
DR Pfam; PF00501; AMP-binding; 1.
DR Pfam; PF00550; PP-binding; 1.
DR Pfam; PF00975; Thioesterase; 1.
DR SMART; SM00823; PKS_PP; 1.
DR SUPFAM; SSF47336; SSF47336; 1.
DR SUPFAM; SSF53474; SSF53474; 1.
DR PROSITE; PS00455; AMP_BINDING; 1.
DR PROSITE; PS50075; CARRIER; 1.
PE 1: Evidence at protein level;
KW Cytoplasm; Phosphopantetheine; Phosphoprotein; Reference proteome;
KW Transferase.
FT CHAIN 1..925
FT /note="Aspulvinone E synthetase melA"
FT /id="PRO_0000448621"
FT DOMAIN 564..644
FT /note="Carrier"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT REGION 11..434
FT /note="Adenylation (A) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:27133313"
FT REGION 663..923
FT /note="Thioesterase (TE) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:27133313"
FT MOD_RES 601
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
SQ SEQUENCE 925 AA; 102373 MW; BFCB718DFBBDFDB8 CRC64;
MQPSLIPSLL ETAAARNGDG RVILYSQGNR EDPRSITYRD LLETASKASV AVHNHQNYTP
GAAVLLHFNN HLDNIVWFWA VLLAGCIPAI TPAFSNNPVQ RVANLEHLSS TLITDWCLTS
QALLVEFAGQ DAIEPVSVET LGWEKASPDS NTASVKAKPT DTALLLFTSG STGKSKAVCL
SHFQIVSAIA GKLSVVPLPE QSSFLNWVGL DHVAAIIEIH LQALYADLDQ VHVPGSDVIS
DPIWFLDLMA THRVSRTFAP NFFLARIRDA LVQNARSASP RQWDLSGLRY VASGGEANTT
KTCDELSQLL KSFGAPLNVI VPGFGMTETC AGAIFNTNCP DYDKKHGLEY TSVGSCMPGI
FMRVTNQQGD PLPPGEMGSL ELAGPVVFRQ YLNNPAATQE SFTMDGWFKT GDCGTLDENG
YLVLGGRAKE TIIINGVKYS PHEIETAVEE HNIKGLSRSF TCCFSSLSPG AETEEIVLVY
LPTYAPEDIP ARAATADAIS KVVLMSTGSR PHIIPLEQAL LPKSTLGKLS RSKIKAAYER
GEYRTHDSIN RSLIARHRQA TRASPKNDFE KGLLEIFLRS FKISEDEFDV QTPIFDVGID
SIELINLKRD IEQHLGFADA TIPIIILLEN TTVRELAAAL DNLYRPKEYN PVVTLQAHGD
KNPLWLVHPG AGEVLIFINL AKFITDRPVY ALRARGFDEG EKPFDSIEDA VTSYYNGVKS
KQPHGPYALA GYCYGSMLAF EVAKKLEENG DEVRFVGSFN LPPHIKMRMR ELDWKECLLH
LAYFLDLITQ KRSRELAVEL DGLDQDTILQ AIIDEADKER YAQLSLSRPF LSRWADVAYE
LHRIAGDYDP DGRVASMDVF FSIPLAIAAA SKSEWRNVHL SQWDDFTRSH VRFHDVPGEH
YSMIGPEHVF AFQKILRSAL AERGM
