AFOF_EMENI
ID AFOF_EMENI Reviewed; 481 AA.
AC Q5BEJ5; C8VTX8;
DT 08-JUN-2016, integrated into UniProtKB/Swiss-Prot.
DT 26-APR-2005, sequence version 1.
DT 25-MAY-2022, entry version 95.
DE RecName: Full=FAD-linked oxidoreductase afoF {ECO:0000305};
DE EC=1.-.-.- {ECO:0000305|PubMed:19199437};
DE AltName: Full=Asperfuranone biosynthesis protein B {ECO:0000303|PubMed:19199437};
DE Flags: Precursor;
GN Name=afoF {ECO:0000303|PubMed:19199437}; ORFNames=AN1035;
OS Emericella nidulans (strain FGSC A4 / ATCC 38163 / CBS 112.46 / NRRL 194 /
OS M139) (Aspergillus nidulans).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Aspergillaceae; Aspergillus;
OC Aspergillus subgen. Nidulantes.
OX NCBI_TaxID=227321;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=FGSC A4 / ATCC 38163 / CBS 112.46 / NRRL 194 / M139;
RX PubMed=16372000; DOI=10.1038/nature04341;
RA Galagan J.E., Calvo S.E., Cuomo C., Ma L.-J., Wortman J.R., Batzoglou S.,
RA Lee S.-I., Bastuerkmen M., Spevak C.C., Clutterbuck J., Kapitonov V.,
RA Jurka J., Scazzocchio C., Farman M.L., Butler J., Purcell S., Harris S.,
RA Braus G.H., Draht O., Busch S., D'Enfert C., Bouchier C., Goldman G.H.,
RA Bell-Pedersen D., Griffiths-Jones S., Doonan J.H., Yu J., Vienken K.,
RA Pain A., Freitag M., Selker E.U., Archer D.B., Penalva M.A., Oakley B.R.,
RA Momany M., Tanaka T., Kumagai T., Asai K., Machida M., Nierman W.C.,
RA Denning D.W., Caddick M.X., Hynes M., Paoletti M., Fischer R., Miller B.L.,
RA Dyer P.S., Sachs M.S., Osmani S.A., Birren B.W.;
RT "Sequencing of Aspergillus nidulans and comparative analysis with A.
RT fumigatus and A. oryzae.";
RL Nature 438:1105-1115(2005).
RN [2]
RP GENOME REANNOTATION.
RC STRAIN=FGSC A4 / ATCC 38163 / CBS 112.46 / NRRL 194 / M139;
RX PubMed=19146970; DOI=10.1016/j.fgb.2008.12.003;
RA Wortman J.R., Gilsenan J.M., Joardar V., Deegan J., Clutterbuck J.,
RA Andersen M.R., Archer D., Bencina M., Braus G., Coutinho P., von Dohren H.,
RA Doonan J., Driessen A.J., Durek P., Espeso E., Fekete E., Flipphi M.,
RA Estrada C.G., Geysens S., Goldman G., de Groot P.W., Hansen K.,
RA Harris S.D., Heinekamp T., Helmstaedt K., Henrissat B., Hofmann G.,
RA Homan T., Horio T., Horiuchi H., James S., Jones M., Karaffa L.,
RA Karanyi Z., Kato M., Keller N., Kelly D.E., Kiel J.A., Kim J.M.,
RA van der Klei I.J., Klis F.M., Kovalchuk A., Krasevec N., Kubicek C.P.,
RA Liu B., Maccabe A., Meyer V., Mirabito P., Miskei M., Mos M., Mullins J.,
RA Nelson D.R., Nielsen J., Oakley B.R., Osmani S.A., Pakula T., Paszewski A.,
RA Paulsen I., Pilsyk S., Pocsi I., Punt P.J., Ram A.F., Ren Q., Robellet X.,
RA Robson G., Seiboth B., van Solingen P., Specht T., Sun J.,
RA Taheri-Talesh N., Takeshita N., Ussery D., vanKuyk P.A., Visser H.,
RA van de Vondervoort P.J., de Vries R.P., Walton J., Xiang X., Xiong Y.,
RA Zeng A.P., Brandt B.W., Cornell M.J., van den Hondel C.A., Visser J.,
RA Oliver S.G., Turner G.;
RT "The 2008 update of the Aspergillus nidulans genome annotation: a community
RT effort.";
RL Fungal Genet. Biol. 46:S2-13(2009).
RN [3]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=19199437; DOI=10.1021/ja8088185;
RA Chiang Y.M., Szewczyk E., Davidson A.D., Keller N., Oakley B.R., Wang C.C.;
RT "A gene cluster containing two fungal polyketide synthases encodes the
RT biosynthetic pathway for a polyketide, asperfuranone, in Aspergillus
RT nidulans.";
RL J. Am. Chem. Soc. 131:2965-2970(2009).
RN [4]
RP BIOTECHNOLOGY.
RX PubMed=20148857; DOI=10.1111/j.1742-7843.2010.00545.x;
RA Wang C.C., Chiang Y.M., Praseuth M.B., Kuo P.L., Liang H.L., Hsu Y.L.;
RT "Asperfuranone from Aspergillus nidulans inhibits proliferation of human
RT non-small cell lung cancer A549 cells via blocking cell cycle progression
RT and inducing apoptosis.";
RL Basic Clin. Pharmacol. Toxicol. 107:583-589(2010).
CC -!- FUNCTION: FAD-linked oxidoreductase; part of the gene cluster that
CC mediates the biosynthesis of asperfuranone, a probable antitumor agent
CC (PubMed:19199437). The polyketide synthase afoG is responsible for
CC producing the 3,5-dimethyloctadienone moiety from acetyl-CoA, three
CC malonyl-CoA, and two S-adenosyl methionines (SAM) (PubMed:19199437).
CC The 3,5-dimethyloctadienone moiety is then loaded onto the SAT domain
CC of afoE and extended with four malonyl-CoA and one SAM, which leads to
CC the formation of 2,4-dihydroxy-6-(5,7-dimethyl-2-oxo-trans-3-trans-5-
CC nonadienyl)-3-methylbenzaldehyde (compound 2) after reductive release
CC and aldol condensation (PubMed:19199437). AfoD is the next enzyme in
CC the biosynthesis sequence and hydroxylates the side chain at the
CC benzylic position of compound 2 (PubMed:19199437). After benzylic
CC hydroxylation, a furan ring is formed after five-member ring hemiacetal
CC formation and water elimination (PubMed:19199437). AfoF and afoC are
CC proposed to oxidize the R-diketone proton and to reduce the
CC unconjugated carbonyl group, respectively, to generate asperfuranone
CC (PubMed:19199437). Since no intermediates could be isolated from afoF
CC and afoC deletants, the sequence of these two enzymes is not fully
CC understood (PubMed:19199437). Moreover, since afoC deletant still
CC produces a small amount of asperfuranone, other endogenous
CC oxidoreductases might catalyze the same reaction with much less
CC efficiency (PubMed:19199437). {ECO:0000269|PubMed:19199437}.
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692;
CC Evidence={ECO:0000305|PubMed:19199437};
CC -!- INDUCTION: Expression is regulated by the asperfuranone cluster
CC transcription factor afoA (PubMed:19199437).
CC {ECO:0000269|PubMed:19199437}.
CC -!- DISRUPTION PHENOTYPE: Completely abolishes the production of
CC asperfuranone (PubMed:19199437). {ECO:0000269|PubMed:19199437}.
CC -!- BIOTECHNOLOGY: Asperfuranone provides anti-proliferative activity in
CC human non-small cell lung cancer cells (PubMed:20148857).
CC {ECO:0000269|PubMed:20148857}.
CC -!- SIMILARITY: Belongs to the oxygen-dependent FAD-linked oxidoreductase
CC family. {ECO:0000305}.
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DR EMBL; BN001308; CBF88293.1; -; Genomic_DNA.
DR EMBL; AACD01000015; EAA65603.1; -; Genomic_DNA.
DR RefSeq; XP_658639.1; XM_653547.1.
DR AlphaFoldDB; Q5BEJ5; -.
DR SMR; Q5BEJ5; -.
DR STRING; 162425.CADANIAP00001612; -.
DR PRIDE; Q5BEJ5; -.
DR EnsemblFungi; CBF88293; CBF88293; ANIA_01035.
DR EnsemblFungi; EAA65603; EAA65603; AN1035.2.
DR GeneID; 2876809; -.
DR KEGG; ani:AN1035.2; -.
DR VEuPathDB; FungiDB:AN1035; -.
DR eggNOG; ENOG502SJ3M; Eukaryota.
DR HOGENOM; CLU_018354_0_1_1; -.
DR InParanoid; Q5BEJ5; -.
DR OMA; WVSPATE; -.
DR OrthoDB; 350817at2759; -.
DR Proteomes; UP000000560; Chromosome VIII.
DR Proteomes; UP000005890; Unassembled WGS sequence.
DR GO; GO:0005576; C:extracellular region; IDA:AspGD.
DR GO; GO:0071949; F:FAD binding; IEA:InterPro.
DR GO; GO:0016491; F:oxidoreductase activity; IEA:UniProtKB-KW.
DR GO; GO:1900554; P:asperfuranone biosynthetic process; IMP:AspGD.
DR Gene3D; 3.30.465.10; -; 1.
DR InterPro; IPR012951; BBE.
DR InterPro; IPR016166; FAD-bd_PCMH.
DR InterPro; IPR036318; FAD-bd_PCMH-like_sf.
DR InterPro; IPR016169; FAD-bd_PCMH_sub2.
DR InterPro; IPR006094; Oxid_FAD_bind_N.
DR Pfam; PF08031; BBE; 1.
DR Pfam; PF01565; FAD_binding_4; 1.
DR SUPFAM; SSF56176; SSF56176; 1.
DR PROSITE; PS51387; FAD_PCMH; 1.
PE 1: Evidence at protein level;
KW FAD; Flavoprotein; Glycoprotein; Oxidoreductase; Reference proteome;
KW Signal.
FT SIGNAL 1..16
FT /evidence="ECO:0000255"
FT CHAIN 17..481
FT /note="FAD-linked oxidoreductase afoF"
FT /evidence="ECO:0000255"
FT /id="PRO_5006966312"
FT DOMAIN 52..227
FT /note="FAD-binding PCMH-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00718"
FT MOD_RES 92
FT /note="Pros-8alpha-FAD histidine"
FT /evidence="ECO:0000255"
FT CARBOHYD 82
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 196
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 241
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 276
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 309
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 312
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 376
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ SEQUENCE 481 AA; 52262 MW; 78CF492376141AF7 CRC64;
MRFLLQSITL VAAARAASID LESLFGPYVS PETEIAEVGD ADFDEVVSPR WSEWRPPTWT
GAIKPQTEED LQEIVRIAVA NNVSFMATSG GHGTSLIYGT VKGLDINLAN FNNVDIDLES
NTVTVGAGAK LGDITEPLYK AGKAIQTARG NSPCVGVIGA TIGGGIGYET GLFGLGVDAL
VSVRIITATG ELITANETCN SDLLWAIRGA GANFGIITAA TFKMFDQPNN GDAVIGTFVY
NSSKSLGVFE YLSVLDNVLP PELGVQLSIG YDRTINETLL TVDIKHFAPW ATFVDHWEHA
EALGPISRNV SNVTLVELYA GLDGPCQTGA YVSGGTVGLG RTDAATMQEV FDDMTAFYEQ
YPGYLGQSLF QRYANNNTLK TPAHTAVYPW RDTKMFWLHE NIFLNPELEA PTNELLVSLR
EKLHATSGFP ADQPHIYVNY AFGDEGPEAW WSKENLPKLS YLKRKWDPKG VFGKGTPIPR
F
