ID   AUSF_EMENI              Reviewed;         177 AA.
AC   Q5AR33; C8VQ84;
DT   08-JUN-2016, integrated into UniProtKB/Swiss-Prot.
DT   26-APR-2005, sequence version 1.
DT   25-MAY-2022, entry version 67.
DE   RecName: Full=Austinoid biosynthesis clusters protein F {ECO:0000303|PubMed:22329759};
GN   Name=ausF {ECO:0000303|PubMed:22329759}; ORFNames=AN9247;
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.
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: Part of the gene cluster B that mediates the biosynthesis of
CC       austinol and dehydroaustinol, two fungal meroterpenoids
CC       (PubMed:22329759). The first step of the pathway is the synthesis of
CC       3,5-dimethylorsellinic acid by the polyketide synthase ausA
CC       (PubMed:22329759). 3,5-dimethylorsellinic acid is then prenylated by
CC       the polyprenyl transferase ausN (PubMed:22329759). Further epoxidation
CC       by the FAD-dependent monooxygenase ausM and cyclization by the probable
CC       terpene cyclase ausL lead to the formation of protoaustinoid A
CC       (PubMed:22329759). Protoaustinoid A is then oxidized to spiro-lactone
CC       preaustinoid A3 by the combined action of the FAD-binding
CC       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   -!- PATHWAY: Secondary metabolite biosynthesis; terpenoid biosynthesis.
CC       {ECO:0000269|PubMed:22329759}.
CC   -!- SUBUNIT: Homodimer. {ECO:0000250|UniProtKB:Q5AR31}.
CC   -!- DISRUPTION PHENOTYPE: Strongly decreases the production 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 trt14 isomerase family. {ECO:0000305}.
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DR   EMBL; BN001308; CBF87241.1; -; Genomic_DNA.
DR   EMBL; AACD01000172; EAA66314.1; -; Genomic_DNA.
DR   RefSeq; XP_682516.1; XM_677424.1.
DR   AlphaFoldDB; Q5AR33; -.
DR   SMR; Q5AR33; -.
DR   EnsemblFungi; CBF87241; CBF87241; ANIA_09247.
DR   EnsemblFungi; EAA66314; EAA66314; AN9247.2.
DR   GeneID; 2867898; -.
DR   KEGG; ani:AN9247.2; -.
DR   eggNOG; ENOG502S4TQ; Eukaryota.
DR   HOGENOM; CLU_108113_3_0_1; -.
DR   InParanoid; Q5AR33; -.
DR   OMA; NEYMIVL; -.
DR   OrthoDB; 1409451at2759; -.
DR   UniPathway; UPA00213; -.
DR   Proteomes; UP000000560; Chromosome VIII.
DR   Proteomes; UP000005890; Unassembled WGS sequence.
DR   GO; GO:0016114; P:terpenoid biosynthetic process; IEA:UniProtKB-UniPathway.
DR   InterPro; IPR032710; NTF2-like_dom_sf.
DR   SUPFAM; SSF54427; SSF54427; 1.
PE   3: Inferred from homology;
KW   Reference proteome.
FT   CHAIN           1..177
FT                   /note="Austinoid biosynthesis clusters protein F"
FT                   /id="PRO_0000436487"
SQ   SEQUENCE   177 AA;  20635 MW;  0F9863D82AB470F5 CRC64;
     MTPISVILVT DNKLTRPKTM STTREKLLRT TSRFVSTFGS FDIEEILSIR TPTCLYHQCC
     PSFNKNVVTN EETRANFPQF IATFKRFDFS IIEPDHTLVD EAARRVMIRA KASAESIVGA
     YENEYIFILK MTDDCRFIEE IYEFYDTIRL KDLQYRLEAK HISYGDAAPF KTRDTQL