ID   ACRC_ASPA1              Reviewed;         428 AA.
AC   P9WEZ7; A0A1L9WR54;
DT   12-AUG-2020, integrated into UniProtKB/Swiss-Prot.
DT   12-AUG-2020, sequence version 1.
DT   25-MAY-2022, entry version 4.
DE   RecName: Full=Hydrolase acrC {ECO:0000303|PubMed:32234543};
DE            EC=3.7.1.- {ECO:0000305|PubMed:32234543};
DE   AltName: Full=Acurin A biosynthesis cluster protein C {ECO:0000303|PubMed:32234543};
GN   Name=acrC {ECO:0000303|PubMed:32234543}; ORFNames=ASPACDRAFT_61993-1;
OS   Aspergillus aculeatus (strain ATCC 16872 / CBS 172.66 / WB 5094).
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC   Eurotiomycetidae; Eurotiales; Aspergillaceae; Aspergillus;
OC   Aspergillus subgen. Circumdati.
OX   NCBI_TaxID=690307;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC 16872 / CBS 172.66 / WB 5094;
RX   PubMed=28196534; DOI=10.1186/s13059-017-1151-0;
RA   de Vries R.P., Riley R., Wiebenga A., Aguilar-Osorio G., Amillis S.,
RA   Uchima C.A., Anderluh G., Asadollahi M., Askin M., Barry K., Battaglia E.,
RA   Bayram O., Benocci T., Braus-Stromeyer S.A., Caldana C., Canovas D.,
RA   Cerqueira G.C., Chen F., Chen W., Choi C., Clum A., Dos Santos R.A.,
RA   Damasio A.R., Diallinas G., Emri T., Fekete E., Flipphi M., Freyberg S.,
RA   Gallo A., Gournas C., Habgood R., Hainaut M., Harispe M.L., Henrissat B.,
RA   Hilden K.S., Hope R., Hossain A., Karabika E., Karaffa L., Karanyi Z.,
RA   Krasevec N., Kuo A., Kusch H., LaButti K., Lagendijk E.L., Lapidus A.,
RA   Levasseur A., Lindquist E., Lipzen A., Logrieco A.F., MacCabe A.,
RA   Maekelae M.R., Malavazi I., Melin P., Meyer V., Mielnichuk N., Miskei M.,
RA   Molnar A.P., Mule G., Ngan C.Y., Orejas M., Orosz E., Ouedraogo J.P.,
RA   Overkamp K.M., Park H.-S., Perrone G., Piumi F., Punt P.J., Ram A.F.,
RA   Ramon A., Rauscher S., Record E., Riano-Pachon D.M., Robert V., Roehrig J.,
RA   Ruller R., Salamov A., Salih N.S., Samson R.A., Sandor E., Sanguinetti M.,
RA   Schuetze T., Sepcic K., Shelest E., Sherlock G., Sophianopoulou V.,
RA   Squina F.M., Sun H., Susca A., Todd R.B., Tsang A., Unkles S.E.,
RA   van de Wiele N., van Rossen-Uffink D., Oliveira J.V., Vesth T.C.,
RA   Visser J., Yu J.-H., Zhou M., Andersen M.R., Archer D.B., Baker S.E.,
RA   Benoit I., Brakhage A.A., Braus G.H., Fischer R., Frisvad J.C.,
RA   Goldman G.H., Houbraken J., Oakley B., Pocsi I., Scazzocchio C.,
RA   Seiboth B., vanKuyk P.A., Wortman J., Dyer P.S., Grigoriev I.V.;
RT   "Comparative genomics reveals high biological diversity and specific
RT   adaptations in the industrially and medically important fungal genus
RT   Aspergillus.";
RL   Genome Biol. 18:RESEARCH28.1-RESEARCH28.45(2017).
RN   [2]
RP   FUNCTION, DISRUPTION PHENOTYPE, PATHWAY, AND INDUCTION.
RX   PubMed=32234543; DOI=10.1016/j.fgb.2020.103378;
RA   Wolff P.B., Nielsen M.L., Slot J.C., Andersen L.N., Petersen L.M.,
RA   Isbrandt T., Holm D.K., Mortensen U.H., Noedvig C.S., Larsen T.O.,
RA   Hoof J.B.;
RT   "Acurin A, a novel hybrid compound, biosynthesized by individually
RT   translated PKS- and NRPS-encoding genes in Aspergillus aculeatus.";
RL   Fungal Genet. Biol. 139:103378-103378(2020).
CC   -!- FUNCTION: Hydrolase; part of the cluster that mediates the biosynthesis
CC       of acurin A, a highly reduced polyketide coupled to a serine via a
CC       peptide bond (PubMed:32234543). The activities of the highly reducing
CC       polyketide synthase acrA and the nonribosomal peptide synthetase acrB
CC       are collectively responsible for the synthesis of the acurin A core
CC       structure with a heptaketide backbone produced by acrA covalently fused
CC       to a L-serine by acrB (PubMed:32234543). After the formation of the PK-
CC       NRP hybrid product, it is detached from acrB by reductive release to
CC       set up the formation of the lactam ring by aldol condensation
CC       (Probable). The hydrolyase acrC then catalyzes water loss to generate a
CC       double bond in the ring (Probable). This double bond is probably
CC       reduced, which is followed by three oxidations at C-22 to generate the
CC       carboxylic acid moiety, involving probably the FAD-binding
CC       monooxygenase acrE and the cytochrome P450 monooxygenases acrD and acrF
CC       (Probable). Finally, a last methylation step performed by the O-
CC       methyltransferase acrG leads to the production of acurin A (Probable).
CC       {ECO:0000269|PubMed:32234543, ECO:0000305|PubMed:32234543}.
CC   -!- PATHWAY: Secondary metabolite biosynthesis.
CC       {ECO:0000269|PubMed:32234543}.
CC   -!- INDUCTION: Expression is positively regulated by the acurin A cluster-
CC       specific transcription regulator acrR. {ECO:0000269|PubMed:32234543}.
CC   -!- DISRUPTION PHENOTYPE: Abolishes the production of acurin A.
CC       {ECO:0000269|PubMed:32234543}.
CC   -!- SIMILARITY: Belongs to the AB hydrolase superfamily. FUS2 hydrolase
CC       family. {ECO:0000305}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=OJJ98487.1; Type=Erroneous gene model prediction; Note=The predicted gene ASPACDRAFT_61993 has been split into 2 genes: ASPACDRAFT_61993-1 and ASPACDRAFT_61993-2.; Evidence={ECO:0000305};
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DR   EMBL; KV878980; OJJ98487.1; ALT_SEQ; Genomic_DNA.
DR   AlphaFoldDB; P9WEZ7; -.
DR   SMR; P9WEZ7; -.
DR   EnsemblFungi; OJJ98487; OJJ98487; ASPACDRAFT_61993.
DR   Proteomes; UP000184546; Unassembled WGS sequence.
DR   GO; GO:0016787; F:hydrolase activity; IEA:UniProtKB-KW.
DR   Gene3D; 3.40.50.1820; -; 1.
DR   InterPro; IPR029058; AB_hydrolase.
DR   InterPro; IPR000073; AB_hydrolase_1.
DR   Pfam; PF12697; Abhydrolase_6; 1.
DR   SUPFAM; SSF53474; SSF53474; 1.
PE   2: Evidence at transcript level;
KW   Hydrolase; Reference proteome.
FT   CHAIN           1..428
FT                   /note="Hydrolase acrC"
FT                   /id="PRO_0000450419"
FT   ACT_SITE        248
FT                   /evidence="ECO:0000250|UniProtKB:Q93NG6"
SQ   SEQUENCE   428 AA;  47714 MW;  9499702C5CA241E6 CRC64;
     MFKFYPSDFF HFEFLRVLAS APAGGAETGE CLAVLPQVPD GDAEAWYRAW TAQAQQARGL
     GDEALVSGDT VAASGAYLRA SNYFRASEFF LHTRPDDPRL LAAMENSVAV FDKGVDLLDT
     CTVVRVEIPY EEEKGAARLP GRLYLPRSGA AQTGQGQSED KLPLLIMTGG FDSTQEELYF
     FGPAAALPRG YAVLTFEGPG QGICLRRDGL RLRPDWEHVT TKVLDVVESQ LAKDYPIDLE
     RVAVVGASLG GYFALRAAAD PRVRACVSCD ACYDLFDVTR SRMPGWFING WLSRRLSDGF
     FNWVVNKLAG WSFQLRWEFG HSMWVYGVES PAEVMRCMQQ YHARGYLQKV KCSTFVTGAA
     DTFYFTPKQN TEPIFEALGH VPLQKKRLWI GKGVEGGGLQ AKIGAWAVFH QKMFVWLDEQ
     FEIKRGTI