AUSD_PENBI
ID AUSD_PENBI Reviewed; 279 AA.
AC A0A0F7U1Z8;
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=Methyltransferase ausD {ECO:0000303|PubMed:29076725};
DE EC=2.1.3.- {ECO:0000305|PubMed:29076725};
DE AltName: Full=Austinoid biosynthesis clusters protein D {ECO:0000303|PubMed:29076725};
GN Name=ausD {ECO:0000303|PubMed:29076725}; ORFNames=PMG11_09857;
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: Methyltransferase; part of the gene cluster A that mediates
CC the biosynthesis of the fungal meroterpenoid acetoxydehydroaustin
CC (PubMed:29076725). The first step of the pathway is the synthesis of
CC 3,5-dimethylorsellinic acid by the polyketide synthase ausA (By
CC similarity). 3,5-dimethylorsellinic acid is then prenylated by the
CC polyprenyl transferase ausN (By similarity). Further epoxidation by the
CC 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 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:C8VE82, ECO:0000269|PubMed:29076725}.
CC -!- PATHWAY: Secondary metabolite biosynthesis; terpenoid biosynthesis.
CC {ECO:0000305|PubMed:29076725}.
CC -!- SUBUNIT: Homodimer. {ECO:0000250|UniProtKB:Q3J7D1}.
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 class I-like SAM-binding methyltransferase
CC superfamily. {ECO:0000305}.
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DR EMBL; CDHK01000010; CEJ61322.1; -; Genomic_DNA.
DR SMR; A0A0F7U1Z8; -.
DR STRING; 104259.A0A0F7U1Z8; -.
DR EnsemblFungi; CEJ61322; CEJ61322; PMG11_09857.
DR OrthoDB; 1471762at2759; -.
DR UniPathway; UPA00213; -.
DR Proteomes; UP000042958; Unassembled WGS sequence.
DR GO; GO:0008168; F:methyltransferase activity; IEA:UniProtKB-KW.
DR GO; GO:0032259; P:methylation; IEA:UniProtKB-KW.
DR GO; GO:0016114; P:terpenoid biosynthetic process; IEA:UniProtKB-UniPathway.
DR Gene3D; 3.40.50.150; -; 1.
DR InterPro; IPR029063; SAM-dependent_MTases_sf.
DR SUPFAM; SSF53335; SSF53335; 1.
PE 3: Inferred from homology;
KW Methyltransferase; Reference proteome; S-adenosyl-L-methionine;
KW Transferase.
FT CHAIN 1..279
FT /note="Methyltransferase ausD"
FT /id="PRO_0000453851"
FT BINDING 124..125
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:Q3J7D1"
FT BINDING 152..153
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:Q3J7D1"
SQ SEQUENCE 279 AA; 31788 MW; 33E898D638BE1604 CRC64;
MHPDAQLKTA LKNGFDPKLL YKEPLTTVKE PVCSILEKHS KVPVDKVVSH VNEVRDRAFA
VFPYACIGQF SFVELSIADS PCYREMLERT KQGHKLLDLG CAFGQELRQL IYDGTPPTNL
YGSDIQQDFL NLGYELFLDR AILPDSQLIA ADVLDKQSAL FERLAGELNI VYISLFLHVF
DFEKQITVAQ NVLDLLKAEP GSMIVCRVTA CRDQEVLAAT QERMPYYYHD LASWNRLWEE
VKKQTGVKLS VESWEQPDEL VKKHPLPGIY ILGSSIRRL
