ID   MELA_ASPTE              Reviewed;         925 AA.
AC   A0A336U965;
DT   11-DEC-2019, integrated into UniProtKB/Swiss-Prot.
DT   10-OCT-2018, sequence version 1.
DT   03-AUG-2022, entry version 14.
DE   RecName: Full=Aspulvinone E synthetase melA {ECO:0000303|PubMed:27133313};
DE            EC=2.3.1.- {ECO:0000269|PubMed:27133313};
DE   AltName: Full=Nonribosomal peptide synthetase melA {ECO:0000303|PubMed:27133313};
GN   Name=melA {ECO:0000303|PubMed:27133313};
OS   Aspergillus terreus.
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC   Eurotiomycetidae; Eurotiales; Aspergillaceae; Aspergillus;
OC   Aspergillus subgen. Circumdati.
OX   NCBI_TaxID=33178;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], INDUCTION, DISRUPTION PHENOTYPE,
RP   FUNCTION, AND CATALYTIC ACTIVITY.
RC   STRAIN=SBUG844;
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   [2]
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   [3]
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:23841722, PubMed:27133313, PubMed:29270299). The nonribosomal
CC       peptide synthase melA converts 4-hydroxyphenylpyruvate (4-HPPA) to
CC       aspulvinone E (PubMed:27133313, PubMed:29270299). The tyrosinase tyrP
CC       then performs hydroxylations of both aromatic moieties of aspulvinone E
CC       (PubMed:27133313). 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}.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:29270299}.
CC   -!- INDUCTION: Expression is induced during conidiation.
CC       {ECO:0000269|PubMed:27133313}.
CC   -!- DOMAIN: MelA has a A-T-TE domain architecture. The adenylation (A)
CC       domain recognizes and activates the aryl acid substrates, and loads
CC       them onto the thiolation (T) domain. The thioesterase (TE) domain
CC       shares the missing condensation (C) domain function, and is responsible
CC       for condensation and final product release.
CC       {ECO:0000269|PubMed:27133313}.
CC   -!- DISRUPTION PHENOTYPE: Results in white conidia.
CC       {ECO:0000269|PubMed:23841722, ECO:0000269|PubMed:27133313}.
CC   -!- SIMILARITY: Belongs to the ATP-dependent AMP-binding enzyme family.
CC       {ECO:0000305}.
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DR   EMBL; KU530117; AND66115.1; -; Genomic_DNA.
DR   AlphaFoldDB; A0A336U965; -.
DR   SMR; A0A336U965; -.
DR   VEuPathDB; FungiDB:ATEG_03563; -.
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; Transferase.
FT   CHAIN           1..925
FT                   /note="Aspulvinone E synthetase melA"
FT                   /id="PRO_0000448622"
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;  102287 MW;  276C3B3A24B594D0 CRC64;
     MQPSLIPSLL ETAAARNGDG RVILYSQGNR EDPRSITYRD LLETASKASV AVHNHQNYTP
     GAAVLLHFNN HLDNIVWFWA VLLAGCIPAI TPAFSNNPVQ RVANLEHLSS TLITDWCLTS
     QALLAEFAGQ DAIEPVSVET LGWEKASPAS NTASVKAKPT DTALLLFTSG STGKSKAVCL
     SHFQIVSAIA GKLSVVPLPE QSSFLNWVGL DHVAAIIEIH LQALYADLDQ VHVPGSDVIS
     DPIWFLDLMA THRVSRTFAP NFFLARIRDA LVQNARSASP RQWDLSGLRY VASGGEANTT
     KTCDDLSQLL 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