ID   ACUE_ASPA1              Reviewed;         352 AA.
AC   A0A1L9WN23;
DT   12-AUG-2020, integrated into UniProtKB/Swiss-Prot.
DT   15-MAR-2017, sequence version 1.
DT   25-MAY-2022, entry version 15.
DE   RecName: Full=Oxidoreductase acuE {ECO:0000303|PubMed:26374386};
DE            EC=1.-.-.- {ECO:0000305|PubMed:26374386};
DE   AltName: Full=Aculin biosynthesis cluster protein E {ECO:0000303|PubMed:26374386};
GN   Name=acuE {ECO:0000303|PubMed:26374386}; ORFNames=ASPACDRAFT_1904400;
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, AND PATHWAY.
RX   PubMed=26374386; DOI=10.1002/cbic.201500210;
RA   Petersen L.M., Holm D.K., Gotfredsen C.H., Mortensen U.H., Larsen T.O.;
RT   "Investigation of a 6-MSA Synthase Gene Cluster in Aspergillus aculeatus
RT   Reveals 6-MSA-derived Aculinic Acid, Aculins A-B and Epi-Aculin A.";
RL   ChemBioChem 16:2200-2204(2015).
CC   -!- FUNCTION: Oxidoreductase; part of the gene cluster that mediates the
CC       biosynthesis of aculins (PubMed:26374386). The pathway begins with the
CC       synthesis of 6-methylsalicylic acid by the polyketide synthase (PKS)
CC       acuA via condensation of acetate and malonate units (PubMed:26374386).
CC       The 6-methylsalicylic acid decarboxylase acuB then catalyzes the
CC       decarboxylation of 6-methylsalicylic acid to yield m-cresol (also known
CC       as 3-methylphenol) (Probable). These first reactions occur in the
CC       cytosol (By similarity). The intermediate m-cresol is then transported
CC       into the endoplasmic reticulum where the cytochrome P450 monooxygenase
CC       acuC converts it to m-hydroxybenzyl alcohol, which is further converted
CC       to gentisyl alcohol by the cytochrome P450 monooxygenase acuD
CC       (Probable). Gentisyl alcohol is further oxidized by the oxidoreductase
CC       acuE that probably catalyzes hydroxylation of the aromatic ring
CC       (Probable). The aromatic system might then be opened by oxidation
CC       through a Baeyer-Villiger type of oxidation, which could be catalyzed
CC       by acuF, with the carboxylic acid at C-1 subsequently reduced to an
CC       aldehyde by acuG (Probable). Subsequently, a hemiacetal is formed,
CC       before the dehydrogenase acuH would reduce the double bond between C-4
CC       and C-6 (Probable). Finally, keto-enol tautomerism results in formation
CC       of aculinic acid, which exists as two diastereomers (both R/S
CC       configurations at C-1) by non-enzymatic hemiacetal formation
CC       (Probable). The carboxypeptidase acuI could be involved in the linking
CC       of aculinic acid to an aculene A moiety produced by the aculene
CC       biosynthesis cluster and which leads to the production of aculin A
CC       (Probable). AcuI may also be involved in the attachment of proline to
CC       aculinic acid to form epi-aculins A and B (Probable).
CC       {ECO:0000250|UniProtKB:A0A075TRC0, ECO:0000269|PubMed:26374386,
CC       ECO:0000305|PubMed:26374386}.
CC   -!- PATHWAY: Secondary metabolite biosynthesis.
CC       {ECO:0000305|PubMed:26374386}.
CC   -!- SIMILARITY: Belongs to the oxidoreductase OpS7 family. {ECO:0000305}.
CC   ---------------------------------------------------------------------------
CC   Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC   Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC   ---------------------------------------------------------------------------
DR   EMBL; KV878982; OJJ97579.1; -; Genomic_DNA.
DR   RefSeq; XP_020053919.1; XM_020198808.1.
DR   AlphaFoldDB; A0A1L9WN23; -.
DR   SMR; A0A1L9WN23; -.
DR   EnsemblFungi; OJJ97579; OJJ97579; ASPACDRAFT_1904400.
DR   GeneID; 30972622; -.
DR   VEuPathDB; FungiDB:ASPACDRAFT_1904400; -.
DR   OrthoDB; 1423082at2759; -.
DR   Proteomes; UP000184546; Unassembled WGS sequence.
DR   GO; GO:0016491; F:oxidoreductase activity; IEA:UniProtKB-KW.
DR   Gene3D; 2.60.120.10; -; 1.
DR   InterPro; IPR014710; RmlC-like_jellyroll.
DR   InterPro; IPR011051; RmlC_Cupin_sf.
DR   SUPFAM; SSF51182; SSF51182; 1.
PE   3: Inferred from homology;
KW   Oxidoreductase; Reference proteome.
FT   CHAIN           1..352
FT                   /note="Oxidoreductase acuE"
FT                   /id="PRO_0000450420"
SQ   SEQUENCE   352 AA;  38930 MW;  72358A9C8FB27EF0 CRC64;
     MAPFVPYHNS AGQSKIVKFG GLLTTEFLEP PPGRCFLFRQ TYRHNVEGPI PDNLRKLINS
     PDRPKGPPPH FHQFQTEYFR VESGVMGINV DGQVKRVTAA DGEVSVKAGS VHNFFIHPDS
     EESMTVYLSA SDSGMDYQLD RIFFENWYGY WHDALLHDGG LDWIQFLAIQ DGGDAYTPAP
     AWVPFRRQVG YWTCVIVGRW IGGLLGYKPF FREYTTDWDF AVAKMKGSFF QRHLVHDAYA
     AEKNWDAQVA LEAASRPENA EFEPWVQDMS PKALVLPPVQ YEKGVFVDGA ARATLSGVNG
     HANGVNGHAG VNGHATNGTN GTTTGAEWED VVALKKRVAN GANGVNGTNG VH