ID   ANEE_ASPA1              Reviewed;         318 AA.
AC   A0A1L9WUI4;
DT   26-FEB-2020, integrated into UniProtKB/Swiss-Prot.
DT   15-MAR-2017, sequence version 1.
DT   25-MAY-2022, entry version 20.
DE   RecName: Full=Thiohydrolase aneE {ECO:0000303|PubMed:31618514};
DE            EC=3.1.-.- {ECO:0000269|PubMed:31618514};
DE   AltName: Full=Aculenes biosynthesis cluster protein E {ECO:0000303|PubMed:31618514};
GN   Name=aneE {ECO:0000303|PubMed:31618514}; ORFNames=ASPACDRAFT_78840;
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, CATALYTIC ACTIVITY, AND PATHWAY.
RX   PubMed=31618514; DOI=10.1002/anie.201910200;
RA   Lee C.F., Chen L.X., Chiang C.Y., Lai C.Y., Lin H.C.;
RT   "The biosynthesis of norsesquiterpene aculenes requires three cytochrome
RT   P450 enzymes to catalyze a stepwise demethylation process.";
RL   Angew. Chem. Int. Ed. 58:18414-18418(2019).
CC   -!- FUNCTION: Thiohydrolase; part of the gene cluster that mediates the
CC       biosynthesis of aculenes, a unique type of norsesquiterpenes that
CC       contain a nordaucane skeleton linked to an L-proline moiety and are of
CC       mixed biosynthetic origin (PubMed:31618514). The pathway begins with
CC       the synthesis of dauca-4,7-diene by the terpene cyclase aneC using
CC       farnesyl pyrophosphate (FPP) as substrate (PubMed:31618514). The
CC       cytochrome P450 monooxygenase aneF then performs the initial oxidation
CC       at C-12 of dauca-4,7-diene to yield asperaculane D (PubMed:31618514).
CC       Asperaculane D is substrate of the cytochrome P450 monooxygenase aneD
CC       for C-10 hydroxylation to yield asperaculane E (PubMed:31618514). The
CC       cytochrome P450 monooxygenase aneG then converts asperaculane E into
CC       aculene D via C-2 oxidation (PubMed:31618514). The monomodular
CC       nonribosomal peptide synthtase aneB adenylates L-proline and the
CC       thiohydrolase aneE transfers this activated L-proline derivative to
CC       aculenes D and C to produce respectively aculenes B and A
CC       (PubMed:31618514). The dioxygenase aneA converts aculene D into aculene
CC       C, and aculene B into aculene A by introducing the 5,6-alkene moiety
CC       (PubMed:31618514). Asperculanes A, B, C and F, as well as 14-prolyl
CC       asperculane C, might be shunt products of the pathway
CC       (PubMed:31618514). {ECO:0000269|PubMed:31618514}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=aculene D + L-prolyl-[peptidyl-carrier protein] = aculene B +
CC         holo-[peptidyl-carrier protein]; Xref=Rhea:RHEA:65104, Rhea:RHEA-
CC         COMP:11480, Rhea:RHEA-COMP:14109, ChEBI:CHEBI:64479,
CC         ChEBI:CHEBI:138622, ChEBI:CHEBI:155910, ChEBI:CHEBI:155913;
CC         Evidence={ECO:0000269|PubMed:31618514};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:65105;
CC         Evidence={ECO:0000269|PubMed:31618514};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=aculene C + L-prolyl-[peptidyl-carrier protein] = aculene A +
CC         holo-[peptidyl-carrier protein]; Xref=Rhea:RHEA:65108, Rhea:RHEA-
CC         COMP:11480, Rhea:RHEA-COMP:14109, ChEBI:CHEBI:64479,
CC         ChEBI:CHEBI:138622, ChEBI:CHEBI:155912, ChEBI:CHEBI:155914;
CC         Evidence={ECO:0000269|PubMed:31618514};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:65109;
CC         Evidence={ECO:0000269|PubMed:31618514};
CC   -!- PATHWAY: Secondary metabolite biosynthesis.
CC       {ECO:0000269|PubMed:31618514}.
CC   -!- DISRUPTION PHENOTYPE: Abolishes the production of aculenes A and B and
CC       accumulates aculenes C and D. {ECO:0000269|PubMed:31618514}.
CC   -!- SIMILARITY: Belongs to the polyketide transferase af380 family.
CC       {ECO:0000305}.
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DR   EMBL; KV878977; OJJ99916.1; -; Genomic_DNA.
DR   RefSeq; XP_020056256.1; XM_020205277.1.
DR   AlphaFoldDB; A0A1L9WUI4; -.
DR   SMR; A0A1L9WUI4; -.
DR   ESTHER; aspa1-anee; Thiohydrolase.
DR   EnsemblFungi; OJJ99916; OJJ99916; ASPACDRAFT_78840.
DR   GeneID; 30979091; -.
DR   VEuPathDB; FungiDB:ASPACDRAFT_78840; -.
DR   OrthoDB; 990069at2759; -.
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; IPR022742; Hydrolase_4.
DR   Pfam; PF12146; Hydrolase_4; 1.
DR   SUPFAM; SSF53474; SSF53474; 1.
PE   1: Evidence at protein level;
KW   Hydrolase; Reference proteome.
FT   CHAIN           1..318
FT                   /note="Thiohydrolase aneE"
FT                   /id="PRO_0000449096"
SQ   SEQUENCE   318 AA;  35671 MW;  3F55884F7927A802 CRC64;
     MTKDNEEKTY SEVEFLTVDG LKLRGRLYLG EANGPALVMA HGFNAVKEIV IPWAAEVFQK
     NGISVLLFDP RNYGESEGMP RQEVDPEKQI EDYFDAVTFL RQQPGIDPEA IGLWGVSTSG
     ATAIGAACFD KRVRLIISVC PLIEATFREE MVPDVMAQII REREALVAAR TAGQQSPQPT
     LVPMINQVGV SPMGFNAIHG KNFYEEMPWF KETAPNFRPH TTTLTYYKML RWHPLSNIRC
     LSPTPIQMLI PGKDDVCPTQ EQLDFFEALP GPKRMEYYED RNHHGLLLGS AFEGVMEAQV
     RFVQDVLAGK FALKSGSQ