AUSH_EMENI
ID AUSH_EMENI Reviewed; 174 AA.
AC Q5AR31; C8VQ86;
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 H {ECO:0000303|PubMed:22329759};
GN Name=ausH {ECO:0000303|PubMed:22329759}; ORFNames=AN9249;
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).
RN [7] {ECO:0007744|PDB:5X9K}
RP X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS) OF 46-174, AND SUBUNIT.
RX PubMed=28759016; DOI=10.1038/nchembio.2443;
RA Mori T., Iwabuchi T., Hoshino S., Wang H., Matsuda Y., Abe I.;
RT "Molecular basis for the unusual ring reconstruction in fungal
RT meroterpenoid biogenesis.";
RL Nat. Chem. Biol. 13:1066-1073(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:0000269|PubMed:28759016}.
CC -!- DISRUPTION PHENOTYPE: Impairs the synthesis of austinol and
CC dehydroaustinol and accumulates (5'R)-isoaustinone (PubMed:22329759).
CC {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; CBF87245.1; -; Genomic_DNA.
DR EMBL; AACD01000172; EAA66316.1; -; Genomic_DNA.
DR RefSeq; XP_682518.1; XM_677426.1.
DR PDB; 5X9K; X-ray; 1.80 A; A/B=46-174.
DR PDBsum; 5X9K; -.
DR AlphaFoldDB; Q5AR31; -.
DR SMR; Q5AR31; -.
DR EnsemblFungi; CBF87245; CBF87245; ANIA_09249.
DR EnsemblFungi; EAA66316; EAA66316; AN9249.2.
DR GeneID; 2867899; -.
DR KEGG; ani:AN9249.2; -.
DR VEuPathDB; FungiDB:AN9249; -.
DR eggNOG; ENOG502SZV0; Eukaryota.
DR HOGENOM; CLU_1540028_0_0_1; -.
DR InParanoid; Q5AR31; -.
DR OMA; TDIGPYA; -.
DR OrthoDB; 1409451at2759; -.
DR UniPathway; UPA00213; -.
DR Proteomes; UP000000560; Chromosome VIII.
DR Proteomes; UP000005890; Unassembled WGS sequence.
DR GO; GO:1900560; P:austinol biosynthetic process; IMP:AspGD.
DR GO; GO:1900563; P:dehydroaustinol biosynthetic process; IMP:AspGD.
DR GO; GO:0016114; P:terpenoid biosynthetic process; IEA:UniProtKB-UniPathway.
PE 1: Evidence at protein level;
KW 3D-structure; Reference proteome.
FT CHAIN 1..174
FT /note="Austinoid biosynthesis clusters protein H"
FT /id="PRO_0000436489"
FT HELIX 46..48
FT /evidence="ECO:0007829|PDB:5X9K"
FT HELIX 52..55
FT /evidence="ECO:0007829|PDB:5X9K"
FT STRAND 58..68
FT /evidence="ECO:0007829|PDB:5X9K"
FT STRAND 75..78
FT /evidence="ECO:0007829|PDB:5X9K"
FT HELIX 79..92
FT /evidence="ECO:0007829|PDB:5X9K"
FT STRAND 93..100
FT /evidence="ECO:0007829|PDB:5X9K"
FT STRAND 107..109
FT /evidence="ECO:0007829|PDB:5X9K"
FT TURN 110..113
FT /evidence="ECO:0007829|PDB:5X9K"
FT STRAND 114..125
FT /evidence="ECO:0007829|PDB:5X9K"
FT STRAND 128..140
FT /evidence="ECO:0007829|PDB:5X9K"
FT STRAND 144..154
FT /evidence="ECO:0007829|PDB:5X9K"
FT HELIX 156..173
FT /evidence="ECO:0007829|PDB:5X9K"
SQ SEQUENCE 174 AA; 19411 MW; 7AC90F41D3C2BE70 CRC64;
MVMTNILCQI LSDDLPELPP CREPSKGMIV GNLGMTSNTM TTEGPFAKLD VESVLSFMSP
SCTLRSFPSS LGKPALQTKE ESKADFQGLK DFFYNFQLRV KDGAEPVIDE PARKVVLHIE
GKGDSLVGRF ETEYVYILQI NEEGTMVEDF FQFADSATRD AWGKKIEAHF SARN
