ACRE_ASPA1
ID ACRE_ASPA1 Reviewed; 593 AA.
AC A0A1L9WQQ1;
DT 12-AUG-2020, integrated into UniProtKB/Swiss-Prot.
DT 15-MAR-2017, sequence version 1.
DT 03-AUG-2022, entry version 17.
DE RecName: Full=FAD-binding monooxygenase acrE {ECO:0000303|PubMed:32234543};
DE EC=1.14.13.- {ECO:0000305|PubMed:32234543};
DE AltName: Full=Acurin A biosynthesis cluster protein E {ECO:0000303|PubMed:32234543};
GN Name=acrE {ECO:0000303|PubMed:32234543}; ORFNames=ASPACDRAFT_122285;
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: FAD-binding monooxygenase; part of the cluster that mediates
CC the biosynthesis of acurin A, a highly reduced polyketide coupled to a
CC serine via a peptide bond (PubMed:32234543). The activities of the
CC highly reducing polyketide synthase acrA and the nonribosomal peptide
CC synthetase acrB are collectively responsible for the synthesis of the
CC acurin A core structure with a heptaketide backbone produced by acrA
CC covalently fused to a L-serine by acrB (PubMed:32234543). After the
CC formation of the PK-NRP hybrid product, it is detached from acrB by
CC reductive release to set up the formation of the lactam ring by aldol
CC condensation (Probable). The hydrolyase acrC then catalyzes water loss
CC to generate a double bond in the ring (Probable). This double bond is
CC probably reduced, which is followed by three oxidations at C-22 to
CC generate the 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 -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692;
CC Evidence={ECO:0000250|UniProtKB:H3JQW0};
CC Note=Binds 1 FAD per subunit. {ECO:0000250|UniProtKB:H3JQW0};
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 FAD-binding monooxygenase family.
CC {ECO:0000305}.
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DR EMBL; KV878980; OJJ98492.1; -; Genomic_DNA.
DR RefSeq; XP_020054832.1; XM_020196521.1.
DR AlphaFoldDB; A0A1L9WQQ1; -.
DR SMR; A0A1L9WQQ1; -.
DR STRING; 690307.A0A1L9WQQ1; -.
DR EnsemblFungi; OJJ98492; OJJ98492; ASPACDRAFT_122285.
DR GeneID; 30970335; -.
DR VEuPathDB; FungiDB:ASPACDRAFT_122285; -.
DR OrthoDB; 405736at2759; -.
DR Proteomes; UP000184546; Unassembled WGS sequence.
DR GO; GO:0050660; F:flavin adenine dinucleotide binding; IEA:InterPro.
DR GO; GO:0004499; F:N,N-dimethylaniline monooxygenase activity; IEA:InterPro.
DR GO; GO:0050661; F:NADP binding; IEA:InterPro.
DR Gene3D; 3.50.50.60; -; 2.
DR InterPro; IPR036188; FAD/NAD-bd_sf.
DR InterPro; IPR020946; Flavin_mOase-like.
DR Pfam; PF00743; FMO-like; 1.
DR SUPFAM; SSF51905; SSF51905; 1.
PE 2: Evidence at transcript level;
KW FAD; Flavoprotein; Monooxygenase; NADP; Oxidoreductase; Reference proteome.
FT CHAIN 1..593
FT /note="FAD-binding monooxygenase acrE"
FT /id="PRO_0000450425"
FT BINDING 61..64
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:H3JQW0"
FT BINDING 71..73
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:H3JQW0"
FT BINDING 73..74
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:H3JQW0"
FT BINDING 79
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:H3JQW0"
FT BINDING 200..206
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:H3JQW0"
FT BINDING 223..224
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:H3JQW0"
FT SITE 346
FT /note="Transition state stabilizer"
FT /evidence="ECO:0000250|UniProtKB:H3JQW0"
SQ SEQUENCE 593 AA; 66932 MW; E660C64861D292B4 CRC64;
MHRELKEFSH PHGSTGIYED NLQVDVLIVG AGFSGIYMLH ELRKQGLKTV VYEAGSDLGG
TWRFNCYPGA RVDSQVPLYQ FSIPETYKDW TWSTNYPDYK ELRAYFDHVD KVLDIKKDVA
FGSVVVDAQF DTSQSRWVVK TQDGRTAYAK YFIAAAGVSS KRYIPEWEGI ENFKGPIHHT
SFWPEHEVDV RGKRAAIIGT GASGVQVTQA WGPQAGHLKV FLRSPNYSIP MRRKELTADE
QNQLKPIYPQ LFDLREKTFT GALVDFSERS ALEDSEAERE AFYEQRYQTG GFDFSTANYK
DTMLNPVANR YLYDFWAKKT RARLNDERVK DLLAPVEPPY FFGGKRSSLE TDFYEQFNRD
TVELVDAKSN PIVGFTENGI KMQDGTVHEV DVVCLATGFD TTTGSMINLG VRSIHGTTLQ
EDWSQAAETY LGLTVSGYPN LFHLYGTHAP TLFSQAVTTI EVQGRWIVDA IKQMERQAIR
SINPSREAAH AWKLQIRAFQ NASFFPTVHS TYMGGSIPGK PFELVSYPAG MPMYARQIRD
ALPTFPGFEV VKADGEKVEN LAPGGLEATT NFFERLFGMP PSSAKEDLAK QDH
