AVFA_DOTSN
ID AVFA_DOTSN Reviewed; 284 AA.
AC M2XHE6;
DT 28-FEB-2018, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2013, sequence version 1.
DT 03-AUG-2022, entry version 26.
DE RecName: Full=Averufin oxidase A {ECO:0000250|UniProtKB:Q12437};
DE EC=1.-.-.- {ECO:0000250|UniProtKB:Q12437};
DE AltName: Full=Dothistromin biosynthesis protein avfA {ECO:0000303|PubMed:23207690};
DE Flags: Precursor;
GN Name=avfA {ECO:0000303|PubMed:23207690}; ORFNames=DOTSEDRAFT_75546;
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: Averufin oxidase A; part of the fragmented gene cluster that
CC mediates the biosynthesis of dothistromin (DOTH), a polyketide toxin
CC very similar in structure to the aflatoxin precursor, versicolorin B
CC (PubMed:12039746, PubMed:17683963, PubMed:22069571, PubMed:23207690,
CC PubMed:23448391). The first step of the pathway is the conversion of
CC acetate to norsolorinic acid (NOR) and requires the fatty acid synthase
CC subunits hexA and hexB, as well as the polyketide synthase pksA
CC (PubMed:16649078, PubMed:23207690). PksA combines a hexanoyl starter
CC unit and 7 malonyl-CoA extender units to synthesize the precursor NOR
CC (By similarity). The hexanoyl starter unit is provided to the acyl-
CC carrier protein (ACP) domain by the fungal fatty acid synthase
CC hexA/hexB (By similarity). The second step is the conversion of NOR to
CC averantin (AVN) and requires the norsolorinic acid ketoreductase nor1,
CC which catalyzes the dehydration of norsolorinic acid to form (1'S)-
CC averantin (PubMed:23207690). The cytochrome P450 monooxygenase avnA
CC then catalyzes the hydroxylation of AVN to 5'hydroxyaverantin (HAVN)
CC (PubMed:23207690). The next step is performed by adhA that transforms
CC HAVN to averufin (AVF) (PubMed:23207690). Averufin might then be
CC converted to hydroxyversicolorone by cypX and avfA (PubMed:23207690).
CC Hydroxyversicolorone is further converted versiconal hemiacetal acetate
CC (VHA) by moxY (PubMed:23207690). VHA is then the substrate for the
CC versiconal hemiacetal acetate esterase est1 to yield versiconal (VAL)
CC (PubMed:23207690). Versicolorin B synthase vbsA then converts VAL to
CC versicolorin B (VERB) by closing the bisfuran ring (PubMed:16649078,
CC PubMed:23207690). Then, the activity of the versicolorin B desaturase
CC verB leads to versicolorin A (VERA) (PubMed:23207690). DotB, a
CC predicted chloroperoxidase, may perform epoxidation of the A-ring of
CC VERA (PubMed:23207690). Alternatively, a cytochrome P450, such as cypX
CC or avnA could catalyze this step (PubMed:23207690). It is also possible
CC that another, uncharacterized, cytochrome P450 enzyme is responsible
CC for this step (PubMed:23207690). Opening of the epoxide could
CC potentially be achieved by the epoxide hydrolase epoA
CC (PubMed:23207690). However, epoA seems not to be required for DOTH
CC biosynthesis, but other epoxide hydrolases may have the ability to
CC complement this hydrolysis (PubMed:23207690). Alternatively, opening of
CC the epoxide ring could be achieved non-enzymatically (PubMed:23207690).
CC The next step is the deoxygenation of ring A to yield the 5,8-
CC dihydroxyanthraquinone which is most likely catalyzed by the NADPH
CC dehydrogenase encoded by ver1 (PubMed:23207690). The last stages of
CC DOTH biosynthesis are proposed to involve hydroxylation of the bisfuran
CC (PubMed:23207690). OrdB and norB might have oxidative roles here
CC (PubMed:23207690). An alternative possibility is that cytochrome P450
CC monoogenases such as avnA and cypX might perform these steps in
CC addition to previously proposed steps (PubMed:23207690).
CC {ECO:0000250|UniProtKB:Q12437, ECO:0000269|PubMed:12039746,
CC ECO:0000269|PubMed:16649078, ECO:0000303|PubMed:22069571,
CC ECO:0000305|PubMed:17683963, ECO:0000305|PubMed:23207690,
CC ECO:0000305|PubMed:23448391}.
CC -!- PATHWAY: Mycotoxin biosynthesis. {ECO:0000303|PubMed:22069571,
CC ECO:0000305|PubMed:23207690}.
CC -!- INDUCTION: Expression is positively regulated by the dothistromin-
CC specific transcription factor aflR (PubMed:23207690). Dothistromin
CC biosynthetic proteins are co-regulated, showing a high level of
CC expression at ealy exponential phase with a subsequent decline in older
CC cultures (PubMed:17683963). {ECO:0000269|PubMed:17683963,
CC ECO:0000269|PubMed:23207690}.
CC -!- SIMILARITY: Belongs to the avfA family. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; KB446546; EME38862.1; -; Genomic_DNA.
DR AlphaFoldDB; M2XHE6; -.
DR EnsemblFungi; EME38862; EME38862; DOTSEDRAFT_75546.
DR eggNOG; ENOG502SM0C; Eukaryota.
DR HOGENOM; CLU_090039_0_0_1; -.
DR OMA; GAAMCEI; -.
DR OrthoDB; 1166292at2759; -.
DR Proteomes; UP000016933; Unassembled WGS sequence.
DR GO; GO:0016491; F:oxidoreductase activity; IEA:UniProtKB-KW.
DR GO; GO:0044281; P:small molecule metabolic process; IEA:UniProt.
DR InterPro; IPR016040; NAD(P)-bd_dom.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR Pfam; PF13460; NAD_binding_10; 1.
DR SUPFAM; SSF51735; SSF51735; 1.
PE 2: Evidence at transcript level;
KW Glycoprotein; Oxidoreductase; Reference proteome; Signal.
FT SIGNAL 1..23
FT /evidence="ECO:0000255"
FT CHAIN 24..284
FT /note="Averufin oxidase A"
FT /id="PRO_0000443466"
FT CARBOHYD 62
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 86
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 190
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ SEQUENCE 284 AA; 30716 MW; A3F5B919AFFB7C24 CRC64;
MPTYALLGAT GATGSAILRC LLASPPPDLD LNILVRSKQK LLKSFPTLTT TISPRIHIIQ
GNSTDTIALQ QCLEDASVAF MCVADNASNK GVSLTADTVT AIVTTLGMLR KLHGSAYNAP
TILQLRSASL NPKLSCQVPR LVYNIVSFCL HYSHLDIVKA CEHYEAAAAK GLLSYIYVDP
PTIHDAFGPN RTGHKLISCK PDVCDKQETA LSYADLGAGF VEIASRKEDF LNQPVGVTAT
GKAKETWGVL AGFLFDGAKG RARAWWEEER PMSKPQNLFL YCGM
