ID   AUSH_PENBI              Reviewed;         147 AA.
AC   A0A0F7TRU0;
DT   29-SEP-2021, integrated into UniProtKB/Swiss-Prot.
DT   22-JUL-2015, sequence version 1.
DT   03-AUG-2022, entry version 13.
DE   RecName: Full=Austinoid biosynthesis clusters protein H {ECO:0000303|PubMed:29076725};
GN   Name=ausH {ECO:0000303|PubMed:29076725}; ORFNames=PMG11_06810;
OS   Penicillium brasilianum.
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC   Eurotiomycetidae; Eurotiales; Aspergillaceae; Penicillium.
OX   NCBI_TaxID=104259;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=MG11;
RX   PubMed=26337871; DOI=10.1128/genomea.00724-15;
RA   Horn F., Linde J., Mattern D.J., Walther G., Guthke R., Brakhage A.A.,
RA   Valiante V.;
RT   "Draft genome sequence of the fungus Penicillium brasilianum MG11.";
RL   Genome Announc. 3:0-0(2015).
RN   [2]
RP   FUNCTION.
RX   PubMed=27602587; DOI=10.1021/jacs.6b08424;
RA   Matsuda Y., Iwabuchi T., Fujimoto T., Awakawa T., Nakashima Y., Mori T.,
RA   Zhang H., Hayashi F., Abe I.;
RT   "Discovery of key dioxygenases that diverged the paraherquonin and
RT   acetoxydehydroaustin pathways in Penicillium brasilianum.";
RL   J. Am. Chem. Soc. 138:12671-12677(2016).
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 B that mediates the biosynthesis of
CC       the fungal meroterpenoid acetoxydehydroaustin (PubMed:29076725). The
CC       first step of the pathway is the synthesis of 3,5-dimethylorsellinic
CC       acid by the polyketide synthase ausA (By similarity). 3,5-
CC       dimethylorsellinic acid is then prenylated by the polyprenyl
CC       transferase ausN (By similarity). Further epoxidation by the FAD-
CC       dependent monooxygenase ausM and cyclization by the probable terpene
CC       cyclase ausL lead to the formation of protoaustinoid A (By similarity).
CC       Protoaustinoid A is then oxidized to spiro-lactone preaustinoid A3 by
CC       the combined action of the FAD-binding monooxygenases ausB and ausC,
CC       and the dioxygenase ausE (By similarity). Acid-catalyzed keto-
CC       rearrangement and ring contraction of the tetraketide portion of
CC       preaustinoid A3 by ausJ lead to the formation of preaustinoid A4 (By
CC       similarity). The aldo-keto reductase ausK, with the help of ausH, is
CC       involved in the next step by transforming preaustinoid A4 into
CC       isoaustinone which is in turn hydroxylated by the P450 monooxygenase
CC       ausI to form austinolide (By similarity). The cytochrome P450
CC       monooxygenase ausG then 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:29076725). The cytochrome P450 monooxygenase then converts
CC       dehydroaustin is into 7-dehydrodehydroaustin (PubMed:29076725). The
CC       hydroxylation catalyzed by ausR permits the second O-acetyltransferase
CC       ausQ to add an additional acetyl group to the molecule, leading to the
CC       formation of acetoxydehydroaustin (PubMed:29076725). Due to genetic
CC       rearrangements of the clusters and the subsequent loss of some enzymes,
CC       the end product of the Penicillium brasilianum austinoid biosynthesis
CC       clusters is acetoxydehydroaustin (PubMed:29076725).
CC       {ECO:0000250|UniProtKB:Q5AR31, ECO:0000269|PubMed:29076725}.
CC   -!- PATHWAY: Secondary metabolite biosynthesis; terpenoid biosynthesis.
CC       {ECO:0000305|PubMed:29076725}.
CC   -!- SUBUNIT: Homodimer. {ECO:0000250|UniProtKB:Q5AR31}.
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; CDHK01000006; CEJ58140.1; -; Genomic_DNA.
DR   SMR; A0A0F7TRU0; -.
DR   EnsemblFungi; CEJ58140; CEJ58140; PMG11_06810.
DR   OrthoDB; 1409451at2759; -.
DR   UniPathway; UPA00213; -.
DR   Proteomes; UP000042958; 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..147
FT                   /note="Austinoid biosynthesis clusters protein H"
FT                   /id="PRO_0000453831"
SQ   SEQUENCE   147 AA;  16555 MW;  D356E856E10D4993 CRC64;
     MSPTRDELLC TALDFVAQFA KLDPESVLSF LSPSCTLRSF PSSLGKPPLQ TKEESKADFQ
     GLKDFFHNFQ LRVKDGAEPV VDEPARKVVL HIEGKGDSLV GRFETEYIYI LQMNEEGTMV
     EDFFQFADSA TRDAWGKKIE AHFSAKN