ID   ACRF_ASPA1              Reviewed;         494 AA.
AC   A0A1L9WQW4;
DT   12-AUG-2020, integrated into UniProtKB/Swiss-Prot.
DT   15-MAR-2017, sequence version 1.
DT   03-AUG-2022, entry version 20.
DE   RecName: Full=Cytochrome P450 monooxygenase acrF {ECO:0000303|PubMed:32234543};
DE            EC=1.-.-.- {ECO:0000269|PubMed:32234543};
DE   AltName: Full=Acurin A biosynthesis cluster protein F {ECO:0000303|PubMed:32234543};
GN   Name=acrF {ECO:0000303|PubMed:32234543}; ORFNames=ASPACDRAFT_62004;
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: Cytochrome P450 monooxygenase; part of the cluster that
CC       mediates the biosynthesis of acurin A, a highly reduced polyketide
CC       coupled to a serine via a peptide bond (PubMed:32234543). The
CC       activities of the highly reducing polyketide synthase acrA and the
CC       nonribosomal peptide synthetase acrB are collectively responsible for
CC       the synthesis of the acurin A core structure with a heptaketide
CC       backbone produced by acrA covalently fused to a L-serine by acrB
CC       (PubMed:32234543). After the formation of the PK-NRP hybrid product, it
CC       is detached from acrB by reductive release to set up the formation of
CC       the lactam ring by aldol condensation (Probable). The hydrolyase acrC
CC       then catalyzes water loss to generate a double bond in the ring
CC       (Probable). This double bond is probably reduced, which is followed by
CC       three oxidations at C-22 to generate the carboxylic acid moiety,
CC       involving probably the FAD-binding monooxygenase acrE and the
CC       cytochrome P450 monooxygenases acrD and acrF (Probable). Finally, a
CC       last methylation step performed by the O-methyltransferase acrG leads
CC       to the production of acurin A (Probable). {ECO:0000269|PubMed:32234543,
CC       ECO:0000305|PubMed:32234543}.
CC   -!- COFACTOR:
CC       Name=heme; Xref=ChEBI:CHEBI:30413;
CC         Evidence={ECO:0000250|UniProtKB:P04798};
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 cytochrome P450 family. {ECO:0000305}.
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DR   EMBL; KV878980; OJJ98498.1; -; Genomic_DNA.
DR   RefSeq; XP_020054838.1; XM_020203738.1.
DR   AlphaFoldDB; A0A1L9WQW4; -.
DR   SMR; A0A1L9WQW4; -.
DR   STRING; 690307.A0A1L9WQW4; -.
DR   EnsemblFungi; OJJ98498; OJJ98498; ASPACDRAFT_62004.
DR   GeneID; 30977552; -.
DR   VEuPathDB; FungiDB:ASPACDRAFT_62004; -.
DR   OrthoDB; 1247045at2759; -.
DR   Proteomes; UP000184546; Unassembled WGS sequence.
DR   GO; GO:0020037; F:heme binding; IEA:InterPro.
DR   GO; GO:0005506; F:iron ion binding; IEA:InterPro.
DR   GO; GO:0004497; F:monooxygenase activity; IEA:UniProtKB-KW.
DR   GO; GO:0016705; F:oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen; IEA:InterPro.
DR   GO; GO:0008152; P:metabolic process; IEA:UniProt.
DR   Gene3D; 1.10.630.10; -; 1.
DR   InterPro; IPR001128; Cyt_P450.
DR   InterPro; IPR002403; Cyt_P450_E_grp-IV.
DR   InterPro; IPR036396; Cyt_P450_sf.
DR   Pfam; PF00067; p450; 1.
DR   PRINTS; PR00465; EP450IV.
DR   PRINTS; PR00385; P450.
DR   SUPFAM; SSF48264; SSF48264; 1.
PE   2: Evidence at transcript level;
KW   Heme; Iron; Metal-binding; Monooxygenase; Oxidoreductase;
KW   Reference proteome.
FT   CHAIN           1..494
FT                   /note="Cytochrome P450 monooxygenase acrF"
FT                   /id="PRO_0000450418"
FT   BINDING         420
FT                   /ligand="heme"
FT                   /ligand_id="ChEBI:CHEBI:30413"
FT                   /ligand_part="Fe"
FT                   /ligand_part_id="ChEBI:CHEBI:18248"
FT                   /note="axial binding residue"
FT                   /evidence="ECO:0000250|UniProtKB:P04798"
SQ   SEQUENCE   494 AA;  55901 MW;  E872C95F1AABCE38 CRC64;
     MHVQSKAPKD LHPQAQMTML QRLYKLGDMF TVDTWPLMDQ MYLVANPKLA HQVSQDSSPF
     PKHPMITRFL KPLTGYNSVL AANDAKWKEL RSLFAPGFSN AHLMTMVPLM VEKTEVFCDL
     LSEYAAKHEL FSMEPMAARL TIDIIGIVVL GVDFKSLTRR DELVEAFRHL LDLLPNGQTL
     DINPVTHYLR RKYANTMDNY IRRVLRDRAA NGANKKFRTL MDIAIERYEQ LPNGSLFDCG
     FEQLAVDNLK TFVFAGHDTS STTLSNIYHL LSKHPEVLAK VIEEHDQVLG KDTAAIGQLI
     RDQPSIINKL PYTTAVIRET LRLYPASGSL RMAPKDTTFH PDKAPAVTVP KGSLIWVGIH
     TIHHDAEFFP CPDEFHPERF MTAKTITLAD GRTEAVTAGW NGHAPPADAY RPFEKGPRMC
     IGSEMAMIEI RVVLAMTLRR FRFESAYAEY RRRHPDEVEA AGGRTEAFGD EAYQVFSSTA
     KPKSGVPMYV YTKE