APVA_ASPTN
ID APVA_ASPTN Reviewed; 925 AA.
AC Q0CWD0; A0A2I6SS11;
DT 12-AUG-2020, integrated into UniProtKB/Swiss-Prot.
DT 12-AUG-2020, sequence version 2.
DT 03-AUG-2022, entry version 75.
DE RecName: Full=Nonribosomal peptide synthetase apvA {ECO:0000303|PubMed:23841722};
DE EC=2.3.1.- {ECO:0000269|PubMed:23841722, ECO:0000269|PubMed:28791090, ECO:0000269|PubMed:29305695};
DE AltName: Full=Aspulvinone E synthase {ECO:0000303|PubMed:23841722};
GN Name=apvA {ECO:0000303|PubMed:23841722}; ORFNames=ATEG_02004;
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, CATALYTIC ACTIVITY, AND
RP PATHWAY.
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 DOMAIN, FUNCTION, CATALYTIC ACTIVITY, AND PATHWAY.
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 FUNCTION, CATALYTIC ACTIVITY, DISRUPTION PHENOTYPE, TISSUE SPECIFICITY, AND
RP PATHWAY.
RX PubMed=28791090; DOI=10.1039/c5sc01058f;
RA Guo C.J., Sun W.W., Bruno K.S., Oakley B.R., Keller N.P., Wang C.C.C.;
RT "Spatial regulation of a common precursor from two distinct genes generates
RT metabolite diversity.";
RL Chem. Sci. 6:5913-5921(2015).
CC -!- FUNCTION: Nonribosomal peptide synthetase; part of the gene cluster
CC that mediates the biosynthesis of aspulvinones (PubMed:29305695,
CC PubMed:23841722, PubMed:28791090). The nonribosomal peptide synthetase
CC apvA is responsible for the production of aspulvinone E, the core
CC structure of aspulvinones (PubMed:29305695, PubMed:23841722,
CC PubMed:28791090). ApvA first activates 4-hydroxyphenylpyruvate (HPPA)
CC through its A domain to AMP-HPPA (Probable). The HPPA unit is then
CC loaded to the T domain and eventually transferred to the TE domain
CC (Probable). Upon loading of another HPPA unit to the T domain, the TE
CC domain promotes the enolate formation on the unit attached (Probable).
CC The next step involves head to tail Claisen condensation, followed by
CC the keto-enol tautermerization and a nucleophilic attack on the
CC carbonyl carbon to yield the furanone partial structure (Probable). A
CC spontaneous oxidation at the beta-carbon of the thioester might occur
CC in aerobic condition (Probable). The TE domain then catalyzes the
CC hydrolysis of the thioester, followed by spontaneous decarboxylation,
CC dehydroxylation and keto-enol tautermerization to give the aspulvinone
CC core (Probable). Aspulvinone E is highly unstable and converted to
CC isoaspulvinone E in the presence of light (PubMed:29305695). The
CC structural diversity of the aspulvinones suggests that other tailoring
CC enzymes are involved and have still to be identified (Probable).
CC {ECO:0000269|PubMed:23841722, ECO:0000269|PubMed:28791090,
CC ECO:0000269|PubMed:29305695, ECO:0000305|PubMed:23841722}.
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:23841722,
CC ECO:0000269|PubMed:28791090, ECO:0000269|PubMed:29305695};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:63825;
CC Evidence={ECO:0000269|PubMed:23841722, ECO:0000269|PubMed:28791090,
CC ECO:0000269|PubMed:29305695};
CC -!- PATHWAY: Secondary metabolite biosynthesis.
CC {ECO:0000269|PubMed:23841722, ECO:0000269|PubMed:28791090,
CC ECO:0000269|PubMed:29305695}.
CC -!- TISSUE SPECIFICITY: ApvA specifically produces aspulvinone E in hyphea,
CC in contrast to melA which produces aspulvinone E in conidia where it is
CC converted to UV-protective Asp-melanin. {ECO:0000269|PubMed:28791090}.
CC -!- DOMAIN: ApvA has an 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:23841722, ECO:0000305|PubMed:29305695}.
CC -!- DISRUPTION PHENOTYPE: Abolishes the production of aspulvinone E in
CC hyphae, but not in conidia. {ECO:0000269|PubMed:28791090}.
CC -!- SIMILARITY: Belongs to the NRP synthetase family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=EAU36966.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
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DR EMBL; MG384312; AUO29222.1; -; mRNA.
DR EMBL; CH476596; EAU36966.1; ALT_SEQ; Genomic_DNA.
DR RefSeq; XP_001211182.1; XM_001211182.1.
DR AlphaFoldDB; Q0CWD0; -.
DR SMR; Q0CWD0; -.
DR STRING; 33178.CADATEAP00007412; -.
DR EnsemblFungi; EAU36966; EAU36966; ATEG_02004.
DR GeneID; 4316643; -.
DR eggNOG; KOG1176; Eukaryota.
DR eggNOG; KOG1202; Eukaryota.
DR HOGENOM; CLU_000022_23_6_1; -.
DR OrthoDB; 127131at2759; -.
DR Proteomes; UP000007963; Unassembled WGS sequence.
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; 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 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 Phosphopantetheine; Phosphoprotein; Reference proteome; Transferase.
FT CHAIN 1..925
FT /note="Nonribosomal peptide synthetase apvA"
FT /id="PRO_0000450543"
FT DOMAIN 564..644
FT /note="Carrier"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258,
FT ECO:0000305|PubMed:23841722, ECO:0000305|PubMed:29305695"
FT REGION 15..436
FT /note="Adenylation (A) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:23841722,
FT ECO:0000305|PubMed:29305695"
FT REGION 663..909
FT /note="Thioesterase (TE) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:23841722,
FT ECO:0000305|PubMed:29305695"
FT MOD_RES 601
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
SQ SEQUENCE 925 AA; 102765 MW; 451362D7EC905664 CRC64;
MTLNNLQALL RRVAAREDSG HVVVYGMGNT KAFKSYSYQD LLRVAIKASV ALRKTSDLHP
GSVILLHFDN HWDNIVWFWA ASFAGCLPAI SASFSNDASQ RTAHIERLST TLMHPLCLTN
ERIMADFAGQ DAVQPLAVET LVLNGDVSFE ALPQEHPEPS LSDDALLLFT SGSSGNSKGV
CLSHGQILAS ISGKYAVRPL PDNTSFLNWV GLDHVAAIVE IHLQAMYALK TQVHVPAADI
LSSPATFLQL LEKHRVSRTF APNFFLAKLR DLLQENDSLP EPRRWDLRSL EYVASGGEAN
VTKTCDRLSE YLVAFGAPKD VIVPGFGMTE TCAGSIFNTR CPEYDKSRSA EFASVGTCMP
GISMRVTDLS NNALPSGEIG HLQLTGPVVF KRYFNNTSAT QEAFTPDGWF KTGDMGCIDE
NGCLTLTGRA KENMIINGVN HSPHEIETAL DKIPGLTPSY SCCFSFFPSG GETEEICVVY
LPTYSPDDLA ARAQTADAIS KTVLMSTGSR PHVLPLEREA LPKSSLGKLS RAKIKAAYEK
GEYATYQNAN NELMRRYRES TRAEPQNDLE KTLLEVFTRS LSITDDAFDV KTPIFDVGIN
SVELIRLKRD IEDHLGMAAS AIPMIMLMTH STVRDLATAL EKLQGPREYD PVVTLQSHGH
KNPLWLVHPG AGEVLVFINL AQYIVDRPVY ALRARGFNDG EQPFETIEEA TASYYNGIRS
RQPHGPYALA GYCYGSMLAF EVAKMLESHG EEVRFLGSFN LPPHIKMRMR ELDWKECLLH
LAYFLDLVSQ ERSREMSVEL AGLSHDEILD SVIQNANMER YAELSLNRPL LVRWADVAYE
LHRMAFDYDP AGCVAGMDVF FSIPLAIAAA SKTEWRNVHL SQWEDFTRTV PKFHDVAGEH
YSMIGPDHVF SFQKTLRKAL DERGM
