ASAD_ASPFN
ID ASAD_ASPFN Reviewed; 513 AA.
AC B8N0E9;
DT 20-JUN-2018, integrated into UniProtKB/Swiss-Prot.
DT 03-MAR-2009, sequence version 1.
DT 03-AUG-2022, entry version 59.
DE RecName: Full=Cytochrome P450 monooxygenase asaD {ECO:0000303|PubMed:29674152};
DE EC=1.-.-.- {ECO:0000269|PubMed:29674152};
DE AltName: Full=Aspergillic acid biosynthesis cluster protein D {ECO:0000303|PubMed:29674152};
GN Name=asaD {ECO:0000303|PubMed:29674152}; ORFNames=AFLA_023030;
OS Aspergillus flavus (strain ATCC 200026 / FGSC A1120 / IAM 13836 / NRRL 3357
OS / JCM 12722 / SRRC 167).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Aspergillaceae; Aspergillus;
OC Aspergillus subgen. Circumdati.
OX NCBI_TaxID=332952;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 200026 / FGSC A1120 / IAM 13836 / NRRL 3357 / JCM 12722 / SRRC
RC 167;
RX PubMed=25883274; DOI=10.1128/genomea.00168-15;
RA Nierman W.C., Yu J., Fedorova-Abrams N.D., Losada L., Cleveland T.E.,
RA Bhatnagar D., Bennett J.W., Dean R., Payne G.A.;
RT "Genome sequence of Aspergillus flavus NRRL 3357, a strain that causes
RT aflatoxin contamination of food and feed.";
RL Genome Announc. 3:E0016815-E0016815(2015).
RN [2]
RP IDENTIFICATION WITHIN THE CLUSTER, AND INDUCTION.
RX PubMed=23834374; DOI=10.1111/mpp.12056;
RA Dolezal A.L., Obrian G.R., Nielsen D.M., Woloshuk C.P., Boston R.S.,
RA Payne G.A.;
RT "Localization, morphology and transcriptional profile of Aspergillus flavus
RT during seed colonization.";
RL Mol. Plant Pathol. 14:898-909(2013).
RN [3]
RP FUNCTION, DISRUPTION PHENOTYPE, AND PATHWAY.
RX PubMed=29674152; DOI=10.1016/j.fgb.2018.04.009;
RA Lebar M.D., Cary J.W., Majumdar R., Carter-Wientjes C.H., Mack B.M.,
RA Wei Q., Uka V., De Saeger S., Diana Di Mavungu J.;
RT "Identification and functional analysis of the aspergillic acid gene
RT cluster in Aspergillus flavus.";
RL Fungal Genet. Biol. 116:14-23(2018).
CC -!- FUNCTION: Cytochrome P450 monooxygenase; part of the gene cluster that
CC mediates the biosynthesis of aspergillic acid, a hydroxamic acid-
CC containing pyrazinone with aliphatic side chains that originates from
CC leucine (Leu) and isoleucine (Ile) (PubMed:29674152). Aspergillic acid
CC has antibiotic properties and was shown to be lethal to mice
CC (PubMed:29674152). The first step in the pathway is the production of
CC deoxyaspergillic acid via a condensation between the Ile amine and the
CC Leu carboxylic acid, followed by a reductive release from the protein
CC forming the dipeptide aldehyde NH(2)-Leu-Ile-CHO, which could undergo
CC an intermolecular cyclization resulting in a dihydropyrazinone
CC (PubMed:29674152). As the NRPS asaC lacks a condensation domain, it is
CC improbable that it is responsible for condensation of Leu and Ile
CC (PubMed:29674152). One possibility is that asaC acts on a previously
CC condensed dipeptide and functions as a Leu-Ile reductase to yield
CC deoxyaspergillic acid (PubMed:29674152). After asaC forms
CC deoxyaspergillic acid, the cytochrome P450 asaD oxidizes the pyrazinone
CC to the hydroxamic acid-containing bioactive metabolite aspergillic acid
CC (PubMed:29674152). The hydroxylase/desaturase asaB can then convert
CC aspergillic acid to hydroxyaspergillic acid (PubMed:29674152). Both
CC aspergillic acid and hydroxyaspergillic acid can form complexes with
CC iron producing ferriaspergillin analogs (PubMed:29674152).
CC {ECO:0000269|PubMed:29674152}.
CC -!- COFACTOR:
CC Name=heme; Xref=ChEBI:CHEBI:30413;
CC Evidence={ECO:0000250|UniProtKB:P04798};
CC -!- PATHWAY: Secondary metabolite biosynthesis.
CC {ECO:0000269|PubMed:29674152}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000255}; Single-pass membrane
CC protein {ECO:0000255}.
CC -!- INDUCTION: Expressed during the earliest stages of maize kernel
CC infection (PubMed:23834374). {ECO:0000269|PubMed:23834374}.
CC -!- DISRUPTION PHENOTYPE: Blocks the production of aspergillic acid or
CC ferriaspergillin, but accumulates the intermediate deoxyaspergillic
CC acid (PubMed:29674152). {ECO:0000269|PubMed:29674152}.
CC -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
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DR EMBL; EQ963473; EED55032.1; -; Genomic_DNA.
DR RefSeq; XP_002373814.1; XM_002373773.1.
DR AlphaFoldDB; B8N0E9; -.
DR SMR; B8N0E9; -.
DR EnsemblFungi; EED55032; EED55032; AFLA_023030.
DR VEuPathDB; FungiDB:AFLA_023030; -.
DR eggNOG; KOG0156; Eukaryota.
DR HOGENOM; CLU_042557_2_0_1; -.
DR OMA; WPNGQGT; -.
DR Proteomes; UP000001875; Unassembled WGS sequence.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
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 Gene3D; 1.10.630.10; -; 1.
DR InterPro; IPR001128; Cyt_P450.
DR InterPro; IPR017972; Cyt_P450_CS.
DR InterPro; IPR002401; Cyt_P450_E_grp-I.
DR InterPro; IPR036396; Cyt_P450_sf.
DR Pfam; PF00067; p450; 1.
DR PRINTS; PR00463; EP450I.
DR PRINTS; PR00385; P450.
DR SUPFAM; SSF48264; SSF48264; 1.
DR PROSITE; PS00086; CYTOCHROME_P450; 1.
PE 2: Evidence at transcript level;
KW Glycoprotein; Heme; Iron; Membrane; Metal-binding; Monooxygenase;
KW Oxidoreductase; Transmembrane; Transmembrane helix.
FT CHAIN 1..513
FT /note="Cytochrome P450 monooxygenase asaD"
FT /id="PRO_0000444456"
FT TRANSMEM 14..34
FT /note="Helical"
FT /evidence="ECO:0000255"
FT BINDING 461
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"
FT CARBOHYD 258
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 370
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 431
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 441
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ SEQUENCE 513 AA; 58506 MW; E24476DFF4AFACB4 CRC64;
MGFFIQHGLT KPEILYPFLF GIFAVASLCI ATLLFPASFS AASRVISWVL SIYLEVKNPI
RHTETGRNIP GPSYVWPNGQ GDIEKYVQGR SRSEQWQRKY GNVYRIWAGM TPEVVLTRPE
QLHAIFKDSD KHTKATNSDS GYFMSRILGQ CLGLMAGPRW KLLKGIAAPP FMHPTAVRSI
GRIQEHVRAH FHDLETNGNL REGRIHPVQD LKMLPFFIVA EANYGSLTPA MKSELDSLAP
ARENLMKFVL FGGLARFNIS RFFPTEANRQ LRRFRSQWRA FNRAAYERAR EKHPSAMVVQ
MYDAVHKGVL TEEQVAQTMD ETLYANLDVT TGGLSWNLVF LAANPACQAR LHEEISALTP
AEEEGYISRN GTYLAACVLE SSRLRPALPF TIPQSAPTER VVDGYRIPAG TNYVVDTWGL
NVRDEFWAPD NSTYRPERFL NSSNTDLRYH FWRFGFGPRQ CIGRYTADVV IRAILLHLVK
HYELQMLEEG DFTQDPECWI THPDLQVKCV RRT
