AVNA_DOTSN
ID AVNA_DOTSN Reviewed; 525 AA.
AC M2YJD1;
DT 28-FEB-2018, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2013, sequence version 1.
DT 03-AUG-2022, entry version 30.
DE RecName: Full=Averantin hydroxylase {ECO:0000250|UniProtKB:Q12732};
DE EC=1.14.14.116 {ECO:0000250|UniProtKB:Q12732};
DE AltName: Full=Cytochrome P450 monooxygenase avnA {ECO:0000305};
DE AltName: Full=Dothistromin biosynthesis protein avnA {ECO:0000303|PubMed:23207690};
GN Name=avnA {ECO:0000303|PubMed:23207690}; ORFNames=DOTSEDRAFT_57312;
OS Dothistroma septosporum (strain NZE10 / CBS 128990) (Red band needle blight
OS fungus) (Mycosphaerella pini).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Dothideomycetes;
OC Dothideomycetidae; Mycosphaerellales; Mycosphaerellaceae; Dothistroma.
OX NCBI_TaxID=675120;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=NZE10 / CBS 128990;
RX PubMed=23209441; DOI=10.1371/journal.pgen.1003088;
RA de Wit P.J.G.M., van der Burgt A., Oekmen B., Stergiopoulos I.,
RA Abd-Elsalam K.A., Aerts A.L., Bahkali A.H., Beenen H.G., Chettri P.,
RA Cox M.P., Datema E., de Vries R.P., Dhillon B., Ganley A.R.,
RA Griffiths S.A., Guo Y., Hamelin R.C., Henrissat B., Kabir M.S.,
RA Jashni M.K., Kema G., Klaubauf S., Lapidus A., Levasseur A., Lindquist E.,
RA Mehrabi R., Ohm R.A., Owen T.J., Salamov A., Schwelm A., Schijlen E.,
RA Sun H., van den Burg H.A., van Ham R.C.H.J., Zhang S., Goodwin S.B.,
RA Grigoriev I.V., Collemare J., Bradshaw R.E.;
RT "The genomes of the fungal plant pathogens Cladosporium fulvum and
RT Dothistroma septosporum reveal adaptation to different hosts and lifestyles
RT but also signatures of common ancestry.";
RL PLoS Genet. 8:E1003088-E1003088(2012).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=NZE10 / CBS 128990;
RX PubMed=23236275; DOI=10.1371/journal.ppat.1003037;
RA Ohm R.A., Feau N., Henrissat B., Schoch C.L., Horwitz B.A., Barry K.W.,
RA Condon B.J., Copeland A.C., Dhillon B., Glaser F., Hesse C.N., Kosti I.,
RA LaButti K., Lindquist E.A., Lucas S., Salamov A.A., Bradshaw R.E.,
RA Ciuffetti L., Hamelin R.C., Kema G.H.J., Lawrence C., Scott J.A.,
RA Spatafora J.W., Turgeon B.G., de Wit P.J.G.M., Zhong S., Goodwin S.B.,
RA Grigoriev I.V.;
RT "Diverse lifestyles and strategies of plant pathogenesis encoded in the
RT genomes of eighteen Dothideomycetes fungi.";
RL PLoS Pathog. 8:E1003037-E1003037(2012).
RN [3]
RP FUNCTION.
RX PubMed=12039746; DOI=10.1128/aem.68.6.2885-2892.2002;
RA Bradshaw R.E., Bhatnagar D., Ganley R.J., Gillman C.J., Monahan B.J.,
RA Seconi J.M.;
RT "Dothistroma pini, a forest pathogen, contains homologs of aflatoxin
RT biosynthetic pathway genes.";
RL Appl. Environ. Microbiol. 68:2885-2892(2002).
RN [4]
RP FUNCTION.
RX PubMed=16649078; DOI=10.1007/s11046-006-0240-5;
RA Bradshaw R.E., Jin H., Morgan B.S., Schwelm A., Teddy O.R., Young C.A.,
RA Zhang S.;
RT "A polyketide synthase gene required for biosynthesis of the aflatoxin-like
RT toxin, dothistromin.";
RL Mycopathologia 161:283-294(2006).
RN [5]
RP FUNCTION, AND INDUCTION.
RX PubMed=17683963; DOI=10.1016/j.fgb.2007.06.005;
RA Zhang S., Schwelm A., Jin H., Collins L.J., Bradshaw R.E.;
RT "A fragmented aflatoxin-like gene cluster in the forest pathogen
RT Dothistroma septosporum.";
RL Fungal Genet. Biol. 44:1342-1354(2007).
RN [6]
RP REVIEW ON FUNCTION, AND PATHWAY.
RX PubMed=22069571; DOI=10.3390/toxins2112680;
RA Schwelm A., Bradshaw R.E.;
RT "Genetics of dothistromin biosynthesis of Dothistroma septosporum: an
RT update.";
RL Toxins 2:2680-2698(2010).
RN [7]
RP FUNCTION, INDUCTION, AND PATHWAY.
RX PubMed=23207690; DOI=10.1016/j.fgb.2012.11.006;
RA Chettri P., Ehrlich K.C., Cary J.W., Collemare J., Cox M.P.,
RA Griffiths S.A., Olson M.A., de Wit P.J., Bradshaw R.E.;
RT "Dothistromin genes at multiple separate loci are regulated by AflR.";
RL Fungal Genet. Biol. 51:12-20(2013).
RN [8]
RP FUNCTION.
RX PubMed=23448391; DOI=10.1111/nph.12161;
RA Bradshaw R.E., Slot J.C., Moore G.G., Chettri P., de Wit P.J.,
RA Ehrlich K.C., Ganley A.R., Olson M.A., Rokas A., Carbone I., Cox M.P.;
RT "Fragmentation of an aflatoxin-like gene cluster in a forest pathogen.";
RL New Phytol. 198:525-535(2013).
CC -!- FUNCTION: Averantin hydroxylase; part of the fragmented gene cluster
CC that mediates the biosynthesis of dothistromin (DOTH), a polyketide
CC toxin very similar in structure to the aflatoxin precursor,
CC versicolorin B (PubMed:12039746, PubMed:17683963, PubMed:22069571,
CC PubMed:23207690, PubMed:23448391). The first step of the pathway is the
CC conversion of acetate to norsolorinic acid (NOR) and requires the fatty
CC acid synthase subunits hexA and hexB, as well as the polyketide
CC synthase pksA (PubMed:16649078, PubMed:23207690). PksA combines a
CC hexanoyl starter unit and 7 malonyl-CoA extender units to synthesize
CC the precursor NOR (By similarity). The hexanoyl starter unit is
CC provided to the acyl-carrier protein (ACP) domain by the fungal fatty
CC acid synthase hexA/hexB (By similarity). The second step is the
CC conversion of NOR to averantin (AVN) and requires the norsolorinic acid
CC ketoreductase nor1, which catalyzes the dehydration of norsolorinic
CC acid to form (1'S)-averantin (PubMed:23207690). The cytochrome P450
CC monooxygenase avnA then catalyzes the hydroxylation of AVN to
CC 5'hydroxyaverantin (HAVN) (PubMed:23207690). The next step is performed
CC by adhA that transforms HAVN to averufin (AVF) (PubMed:23207690).
CC Averufin might then be converted to hydroxyversicolorone by cypX and
CC avfA (PubMed:23207690). Hydroxyversicolorone is further converted
CC versiconal hemiacetal acetate (VHA) by moxY (PubMed:23207690). VHA is
CC then the substrate for the versiconal hemiacetal acetate esterase est1
CC to yield versiconal (VAL) (PubMed:23207690). Versicolorin B synthase
CC vbsA then converts VAL to versicolorin B (VERB) by closing the bisfuran
CC ring (PubMed:16649078, PubMed:23207690). Then, the activity of the
CC versicolorin B desaturase verB leads to versicolorin A (VERA)
CC (PubMed:23207690). DotB, a predicted chloroperoxidase, may perform
CC epoxidation of the A-ring of VERA (PubMed:23207690). Alternatively, a
CC cytochrome P450, such as cypX or avnA could catalyze this step
CC (PubMed:23207690). It is also possible that another, uncharacterized,
CC cytochrome P450 enzyme is responsible for this step (PubMed:23207690).
CC Opening of the epoxide could potentially be achieved by the epoxide
CC hydrolase epoA (PubMed:23207690). However, epoA seems not to be
CC required for DOTH biosynthesis, but other epoxide hydrolases may have
CC the ability to complement this hydrolysis (PubMed:23207690).
CC Alternatively, opening of the epoxide ring could be achieved non-
CC enzymatically (PubMed:23207690). The next step is the deoxygenation of
CC ring A to yield the 5,8-dihydroxyanthraquinone which is most likely
CC catalyzed by the NADPH dehydrogenase encoded by ver1 (PubMed:23207690).
CC The last stages of DOTH biosynthesis are proposed to involve
CC hydroxylation of the bisfuran (PubMed:23207690). OrdB and norB might
CC have oxidative roles here (PubMed:23207690). An alternative possibility
CC is that cytochrome P450 monoogenases such as avnA and cypX might
CC perform these steps in addition to previously proposed steps
CC (PubMed:23207690). {ECO:0000250|UniProtKB:Q12732,
CC ECO:0000269|PubMed:12039746, ECO:0000269|PubMed:16649078,
CC ECO:0000303|PubMed:22069571, ECO:0000305|PubMed:17683963,
CC ECO:0000305|PubMed:23207690, ECO:0000305|PubMed:23448391}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(1'S)-averantin + O2 + reduced [NADPH--hemoprotein reductase]
CC = (1'S,5'R)-5'-hydroxyaverantin + H2O + oxidized [NADPH--hemoprotein
CC reductase]; Xref=Rhea:RHEA:35575, Rhea:RHEA-COMP:11964, Rhea:RHEA-
CC COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15379, ChEBI:CHEBI:57618,
CC ChEBI:CHEBI:58210, ChEBI:CHEBI:71536, ChEBI:CHEBI:77899;
CC EC=1.14.14.116; Evidence={ECO:0000250|UniProtKB:Q12732};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(1'S)-averantin + O2 + reduced [NADPH--hemoprotein reductase]
CC = (1'S,5'S)-5'-hydroxyaverantin + H(+) + H2O + oxidized [NADPH--
CC hemoprotein reductase]; Xref=Rhea:RHEA:35571, Rhea:RHEA-COMP:11964,
CC Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210,
CC ChEBI:CHEBI:77899, ChEBI:CHEBI:77900; EC=1.14.14.116;
CC Evidence={ECO:0000250|UniProtKB:Q12732};
CC -!- COFACTOR:
CC Name=heme; Xref=ChEBI:CHEBI:30413;
CC Evidence={ECO:0000250|UniProtKB:P04798};
CC -!- PATHWAY: Mycotoxin biosynthesis. {ECO:0000303|PubMed:22069571,
CC ECO:0000305|PubMed:23207690}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000255}; Single-pass membrane
CC protein {ECO:0000255}.
CC -!- INDUCTION: Expression is positively regulated by the dothistromin-
CC specific transcription factor aflR (PubMed:23207690).
CC {ECO:0000269|PubMed:23207690}.
CC -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
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DR EMBL; KB446546; EME39031.1; -; Genomic_DNA.
DR AlphaFoldDB; M2YJD1; -.
DR SMR; M2YJD1; -.
DR STRING; 675120.M2YJD1; -.
DR EnsemblFungi; EME39031; EME39031; DOTSEDRAFT_57312.
DR eggNOG; KOG0158; Eukaryota.
DR HOGENOM; CLU_001570_14_11_1; -.
DR OMA; HPWISSI; -.
DR OrthoDB; 1247045at2759; -.
DR Proteomes; UP000016933; Unassembled WGS sequence.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0140395; F:averantin hydroxylase activity; IEA:UniProtKB-EC.
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 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; Reference proteome; Transmembrane; Transmembrane helix.
FT CHAIN 1..525
FT /note="Averantin hydroxylase"
FT /id="PRO_0000443462"
FT TRANSMEM 36..56
FT /note="Helical"
FT /evidence="ECO:0000255"
FT BINDING 462
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 315
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ SEQUENCE 525 AA; 59271 MW; 8BF5FDAE60327BA3 CRC64;
MAPSSAQGLE LLHGYLNLFT PRTGDVSFMR LVSGYVLATF VAGIGALLLW TLTTVFYRLY
LHPLRRYPGP KLWAISRLPY IRSTVKGTIV HDFHRLHKQY GSVVRIAPDE LSYSTPEATK
VIYQSSPELH KDPMHLPPFH NGTPGILAAE EQHHRRYRRL LAYGFSDRGM RAQQPLIQRH
IDLLVKRLSE NSGKGSLDIV EWYNWCTFDI IGDLAFGESF GCLEESKTHE WIASIAGNVK
AIPIINAIRR FKLDWVIPLI APKKLLKMRQ RNAQFTENKV DQRLSHGADR GDLWDGVMDP
KGTKGGMSRQ EMISNGSAIV LAGSETSSTL LSGCTWLLLQ NPDVLAKLKE HVRGSFTDQS
EIDLISVGKL DYMAAVLDEA LRLYPPVPMQ SNRIVNPGGA DIAGQYVPAG TTVAVQQYAA
CRSSDNFRRP DEFLPQRWLE DPEFANDRRA TSQPFSVGPR NCIGRQLAHA EMRLILAKIL
WHFDLELDAP KMGPRDWLSE QGVWILWDKS PLWVRLMPRT LEKSG
