ID   AUSW_ASPCI              Reviewed;         536 AA.
AC   A0A0U5GHH9;
DT   29-SEP-2021, integrated into UniProtKB/Swiss-Prot.
DT   16-MAR-2016, sequence version 1.
DT   23-FEB-2022, entry version 14.
DE   RecName: Full=Austinoid biosynthesis cluster protein W {ECO:0000303|PubMed:28233494};
DE   Flags: Precursor;
GN   Name=ausW {ECO:0000303|PubMed:28233494}; ORFNames=ASPCAL14370;
OS   Aspergillus calidoustus.
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC   Eurotiomycetidae; Eurotiales; Aspergillaceae; Aspergillus;
OC   Aspergillus subgen. Nidulantes.
OX   NCBI_TaxID=454130;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=SF006504;
RX   PubMed=26966204; DOI=10.1128/genomea.00102-16;
RA   Horn F., Linde J., Mattern D.J., Walther G., Guthke R., Scherlach K.,
RA   Martin K., Brakhage A.A., Petzke L., Valiante V.;
RT   "Draft genome sequences of fungus Aspergillus calidoustus.";
RL   Genome Announc. 4:0-0(2016).
RN   [2]
RP   FUNCTION, AND PATHWAY.
RX   PubMed=28233494; DOI=10.1021/acschembio.7b00003;
RA   Valiante V., Mattern D.J., Schueffler A., Horn F., Walther G.,
RA   Scherlach K., Petzke L., Dickhaut J., Guthke R., Hertweck C., Nett M.,
RA   Thines E., Brakhage A.A.;
RT   "Discovery of an Extended Austinoid Biosynthetic Pathway in Aspergillus
RT   calidoustus.";
RL   ACS Chem. Biol. 12:1227-1234(2017).
RN   [3]
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 that mediates the biosynthesis of
CC       calidodehydroaustin, a fungal meroterpenoid (PubMed:28233494,
CC       PubMed:29076725). The first step of the pathway is the synthesis of
CC       3,5-dimethylorsellinic acid by the polyketide synthase ausA
CC       (PubMed:28233494). 3,5-dimethylorsellinic acid is then prenylated by
CC       the polyprenyl transferase ausN (PubMed:28233494). 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 (By
CC       similarity). 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 (By similarity).
CC       Acid-catalyzed keto-rearrangement and ring contraction of the
CC       tetraketide portion of preaustinoid A3 by ausJ lead to the formation of
CC       preaustinoid A4 (By similarity). The aldo-keto reductase ausK, with the
CC       help of ausH, is involved in the next step by transforming preaustinoid
CC       A4 into isoaustinone which is in turn hydroxylated by the P450
CC       monooxygenase ausI to form austinolide (By similarity). The cytochrome
CC       P450 monooxygenase ausG modifies austinolide to austinol (By
CC       similarity). Austinol is further acetylated to austin by the O-
CC       acetyltransferase ausP, which spontaneously changes to dehydroaustin
CC       (PubMed:28233494). The cytochrome P450 monooxygenase ausR then converts
CC       dehydroaustin is into 7-dehydrodehydroaustin (PubMed:28233494). The
CC       hydroxylation catalyzed by ausR permits the O-acetyltransferase ausQ to
CC       add an additional acetyl group to the molecule, leading to the
CC       formation of acetoxydehydroaustin (PubMed:28233494). The short chain
CC       dehydrogenase ausT catalyzes the reduction of the double bond present
CC       between carbon atoms 1 and 2 to convert 7-dehydrodehydroaustin into
CC       1,2-dihydro-7-hydroxydehydroaustin (PubMed:28233494). AusQ catalyzes
CC       not only an acetylation reaction but also the addition of the PKS ausV
CC       diketide product to 1,2-dihydro-7-hydroxydehydroaustin, forming
CC       precalidodehydroaustin (PubMed:28233494). Finally, the iron/alpha-
CC       ketoglutarate-dependent dioxygenase converts precalidodehydroaustin
CC       into calidodehydroaustin (PubMed:28233494).
CC       {ECO:0000250|UniProtKB:Q5ATJ7, ECO:0000269|PubMed:28233494,
CC       ECO:0000269|PubMed:29076725}.
CC   -!- PATHWAY: Secondary metabolite biosynthesis; terpenoid biosynthesis.
CC       {ECO:0000305|PubMed:28233494}.
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}.
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DR   EMBL; CDMC01000024; CEL11267.1; -; Genomic_DNA.
DR   EnsemblFungi; CEL11267; CEL11267; ASPCAL14370.
DR   OrthoDB; 1884104at2759; -.
DR   UniPathway; UPA00213; -.
DR   Proteomes; UP000054771; Unassembled WGS sequence.
DR   GO; GO:0016114; P:terpenoid biosynthetic process; IEA:UniProtKB-UniPathway.
PE   3: Inferred from homology;
KW   Reference proteome; Signal.
FT   SIGNAL          1..19
FT                   /evidence="ECO:0000255"
FT   CHAIN           20..536
FT                   /note="Austinoid biosynthesis cluster protein W"
FT                   /id="PRO_5006857884"
FT   REGION          75..97
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          135..165
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          183..303
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          320..341
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          382..424
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          487..536
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        198..213
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        492..536
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ   SEQUENCE   536 AA;  49325 MW;  F424A376E8DA828E CRC64;
     MKHPTVALLG VGMLGCAAAL PAGQVANGAQ DDPVPAARTA PATAATAPAD FGATSDPSIA
     GTGFPGLAGF PGFPGSGAAQ AGPVHAPSTF GPAAGPAGFQ GLSGGPGFAF PGFGGGSGFG
     FTGFGGMSAF PGIPGFGGLQ GSAPSQAAAA PSTGDSRSGL PGFPGVSGGS GFGFPSFGGM
     SASPSLPGFG GLQGSGPSQA AAAPSTGDSG SGLPGSPGFS GGSGFGFPGF GGMSAGGGAP
     STMGFPGFPG FTGFPGMTGG FGVPGSAPDQ GASTPAQAAS FPAAGRAGNA IPSASSAPAS
     NGMGAAASLH NLQARQFVGT TGHGMVPPAX GSGLPGSPGF SGGSGFGFPG FGGMSAGGGA
     PSTMGFPGFP GFTGFPGMTG GFGVPGSAPD QGASTPAQAA SFPAAGRAGN AIPSASSAPA
     SNGMGAAASL HNLQARQFVG TTGHGMVPPA FHYMFGWPPV IPSAAGAMPN LGTGFNADAF
     GAEFLGGGEM PSPTSTAASV APTANSVPAT GTAEASTSTP VASAATSAVS ATSSAE