AUSC_EMENI
ID AUSC_EMENI Reviewed; 683 AA.
AC C8VE79; Q5ATJ9;
DT 08-JUN-2016, integrated into UniProtKB/Swiss-Prot.
DT 03-NOV-2009, sequence version 1.
DT 03-AUG-2022, entry version 62.
DE RecName: Full=FAD-binding monooxygenase ausC {ECO:0000305};
DE EC=1.14.13.- {ECO:0000269|PubMed:23865690};
DE AltName: Full=Austinoid biosynthesis clusters protein C {ECO:0000303|PubMed:22329759};
GN Name=ausC {ECO:0000303|PubMed:22329759}; ORFNames=AN8381;
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.
RX PubMed=22234162; DOI=10.1021/cb200455u;
RA Rodriguez-Urra A.B., Jimenez C., Nieto M.I., Rodriguez J., Hayashi H.,
RA Ugalde U.;
RT "Signaling the induction of sporulation involves the interaction of two
RT secondary metabolites in Aspergillus nidulans.";
RL ACS Chem. Biol. 7:599-606(2012).
RN [4]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=22329759; DOI=10.1021/ja209809t;
RA Lo H.C., Entwistle R., Guo C.J., Ahuja M., Szewczyk E., Hung J.H.,
RA Chiang Y.M., Oakley B.R., Wang C.C.;
RT "Two separate gene clusters encode the biosynthetic pathway for the
RT meroterpenoids austinol and dehydroaustinol in Aspergillus nidulans.";
RL J. Am. Chem. Soc. 134:4709-4720(2012).
RN [5]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=23865690; DOI=10.1021/ja405518u;
RA Matsuda Y., Awakawa T., Wakimoto T., Abe I.;
RT "Spiro-ring formation is catalyzed by a multifunctional dioxygenase in
RT austinol biosynthesis.";
RL J. Am. Chem. Soc. 135:10962-10965(2013).
RN [6]
RP FUNCTION.
RX PubMed=29076725; DOI=10.1021/acschembio.7b00814;
RA Mattern D.J., Valiante V., Horn F., Petzke L., Brakhage A.A.;
RT "Rewiring of the austinoid biosynthetic pathway in filamentous fungi.";
RL ACS Chem. Biol. 12:2927-2933(2017).
CC -!- FUNCTION: FAD-binding monooxygenase; part of the gene cluster A that
CC mediates the biosynthesis of austinol and dehydroaustinol, two fungal
CC meroterpenoids (PubMed:22329759). The first step of the pathway is the
CC synthesis of 3,5-dimethylorsellinic acid by the polyketide synthase
CC ausA (PubMed:22329759). 3,5-dimethylorsellinic acid is then prenylated
CC by the polyprenyl transferase ausN (PubMed:22329759). Further
CC epoxidation by the FAD-dependent monooxygenase ausM and cyclization by
CC the probable terpene cyclase ausL lead to the formation of
CC protoaustinoid A (PubMed:22329759). Protoaustinoid A is then oxidized
CC to spiro-lactone preaustinoid A3 by the combined action of the FAD-
CC binding monooxygenases ausB and ausC, and the dioxygenase ausE
CC (PubMed:22329759, PubMed:23865690). Acid-catalyzed keto-rearrangement
CC and ring contraction of the tetraketide portion of preaustinoid A3 by
CC ausJ lead to the formation of preaustinoid A4 (PubMed:22329759). The
CC aldo-keto reductase ausK, with the help of ausH, is involved in the
CC next step by transforming preaustinoid A4 into isoaustinone which is in
CC turn hydroxylated by the P450 monooxygenase ausI to form austinolide
CC (PubMed:22329759). Finally, the cytochrome P450 monooxygenase ausG
CC modifies austinolide to austinol (PubMed:22329759). Austinol can be
CC further modified to dehydroaustinol which forms a diffusible complex
CC with diorcinol that initiates conidiation (PubMed:22234162,
CC PubMed:22329759). Due to genetic rearrangements of the clusters and the
CC subsequent loss of some enzymes, the end products of the Emericella
CC nidulans austinoid biosynthesis clusters are austinol and
CC dehydroaustinol, even if additional enzymes, such as the O-
CC acetyltransferase ausQ and the cytochrome P450 monooxygenase ausR are
CC still functional (PubMed:29076725). {ECO:0000269|PubMed:22234162,
CC ECO:0000269|PubMed:22329759, ECO:0000269|PubMed:23865690,
CC ECO:0000269|PubMed:29076725}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=AH2 + O2 + preaustinoid A = A + H2O + preaustinoid A1;
CC Xref=Rhea:RHEA:65168, ChEBI:CHEBI:13193, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:17499, ChEBI:CHEBI:69023,
CC ChEBI:CHEBI:69026; Evidence={ECO:0000269|PubMed:23865690};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:65169;
CC Evidence={ECO:0000269|PubMed:23865690};
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692;
CC Evidence={ECO:0000250|UniProtKB:H3JQW0};
CC Note=Binds 1 FAD per subunit. {ECO:0000250|UniProtKB:H3JQW0};
CC -!- PATHWAY: Secondary metabolite biosynthesis; terpenoid biosynthesis.
CC {ECO:0000269|PubMed:22329759}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000255}; Single-pass membrane
CC protein {ECO:0000255}.
CC -!- DISRUPTION PHENOTYPE: Impairs the synthesis of austinol and
CC dehydroaustinol (PubMed:22329759). {ECO:0000269|PubMed:22329759}.
CC -!- MISCELLANEOUS: In A.calidoustus, the austinoid gene cluster lies on a
CC contiguous DNA region, while clusters from E.nidulans and P.brasilianum
CC are split in their respective genomes. Genetic rearrangements provoked
CC variability among the clusters and E.nidulans produces the least number
CC of austionoid derivatives with the end products austinol and
CC dehydroaustinol, while P.brasilianum can produce until
CC acetoxydehydroaustin, and A.calidoustus produces the highest number of
CC identified derivatives. {ECO:0000305|PubMed:29076725}.
CC -!- SIMILARITY: Belongs to the FAD-binding monooxygenase family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=CBF80424.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
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DR EMBL; BN001305; CBF80424.1; ALT_SEQ; Genomic_DNA.
DR EMBL; AACD01000152; EAA66901.1; -; Genomic_DNA.
DR RefSeq; XP_681650.1; XM_676558.1.
DR AlphaFoldDB; C8VE79; -.
DR SMR; C8VE79; -.
DR PRIDE; C8VE79; -.
DR EnsemblFungi; CBF80424; CBF80424; ANIA_08381.
DR EnsemblFungi; EAA66901; EAA66901; AN8381.2.
DR GeneID; 2868761; -.
DR KEGG; ani:AN8381.2; -.
DR VEuPathDB; FungiDB:AN8381; -.
DR eggNOG; ENOG502SHCE; Eukaryota.
DR HOGENOM; CLU_006937_8_2_1; -.
DR InParanoid; C8VE79; -.
DR OMA; ALKPWYG; -.
DR OrthoDB; 405736at2759; -.
DR UniPathway; UPA00213; -.
DR Proteomes; UP000000560; Chromosome V.
DR Proteomes; UP000005890; Unassembled WGS sequence.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0004497; F:monooxygenase activity; IEA:UniProtKB-KW.
DR GO; GO:1900560; P:austinol biosynthetic process; IMP:AspGD.
DR GO; GO:1900563; P:dehydroaustinol biosynthetic process; IDA:GO_Central.
DR GO; GO:0016114; P:terpenoid biosynthetic process; IEA:UniProtKB-UniPathway.
DR Gene3D; 3.50.50.60; -; 3.
DR InterPro; IPR036188; FAD/NAD-bd_sf.
DR SUPFAM; SSF51905; SSF51905; 1.
PE 1: Evidence at protein level;
KW FAD; Flavoprotein; Glycoprotein; Membrane; Monooxygenase; NADP;
KW Oxidoreductase; Reference proteome; Transmembrane; Transmembrane helix.
FT CHAIN 1..683
FT /note="FAD-binding monooxygenase ausC"
FT /id="PRO_0000436484"
FT TRANSMEM 111..131
FT /note="Helical"
FT /evidence="ECO:0000255"
FT BINDING 150..153
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:H3JQW0"
FT BINDING 160..162
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:H3JQW0"
FT BINDING 162..163
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:H3JQW0"
FT BINDING 168
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:H3JQW0"
FT BINDING 310..316
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:H3JQW0"
FT BINDING 333..334
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:H3JQW0"
FT SITE 452
FT /note="Transition state stabilizer"
FT /evidence="ECO:0000250|UniProtKB:H3JQW0"
FT CARBOHYD 5
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 286
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 525
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 572
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ SEQUENCE 683 AA; 75879 MW; 414FD7A2A1102D41 CRC64;
MYASNKTYPS SRALPCLVEK VEAQHVDGAI RVRITTLEQK DWRQAKAAAV EAKYEAEREI
QLRAHGNVKD IEITRESAFE HFATDPWAQH VGVDIEAQRE RLLAEPGSRK ILIIGAGFGG
LLFAVRLIQT GRFTAEDITM IDSAAGFGGT WYWNRYPGLM CDTESYIYMP LLEETGYMPR
NKYASGNEIR EHAERIAQTY GLATRAMFRT VVEKLDWNEA EKVWTVAGSM LGIANNGQRD
NMMSFQMVSQ FTIMASGSFA SPRVPDYPNI FDYKGKLFHT ARWDYNYTGG SVENPKMLGL
ADKTVAIIGT GASAVQIVPQ LAKYSNKLIV FQRTPAAVDA RNNCPTDPVW WETETQAEGT
GWQKRRQENF NAFTCNEKPL PSVNKVDDGW TRMPSFSILI GGPQGLDPDY VDRMRAVDMN
RQEKIRARAH NIVQSEGSAD LLTPWYPGWC KRPCFHDDYL SAFNLPNVEL VDIRHNGISH
FTANGLVAND IEYELDVIIL STGYTVPVTR ASPSSRANIA VSGRNGTTME AKWANGLATL
HGVMTRDLPN LFFAGTSQAG ACVNLVYALD QNATHVAYIL ANAFDRRPSD SARVIIEPTP
GSEEAWAMQV LQRAAGFRGI AGCTPGYLNG YGMDASSLSP EQQINAARLA AWGEGIASYV
RYLEAWRAKG DLNGIELTFF AKF
