AUSD_ASPCI
ID AUSD_ASPCI Reviewed; 279 AA.
AC A0A0U5GFQ6;
DT 29-SEP-2021, integrated into UniProtKB/Swiss-Prot.
DT 16-MAR-2016, sequence version 1.
DT 03-AUG-2022, entry version 14.
DE RecName: Full=Methyltransferase ausD {ECO:0000303|PubMed:28233494};
DE EC=2.1.3.- {ECO:0000305|PubMed:28233494};
DE AltName: Full=Austinoid biosynthesis cluster protein D {ECO:0000303|PubMed:28233494};
GN Name=ausD {ECO:0000303|PubMed:28233494}; ORFNames=ASPCAL14368;
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: Methyltransferase; part of the gene cluster that mediates the
CC biosynthesis of calidodehydroaustin, a fungal meroterpenoid
CC (PubMed:28233494, PubMed:29076725). The first step of the pathway is
CC the synthesis of 3,5-dimethylorsellinic acid by the polyketide synthase
CC ausA (PubMed:28233494). 3,5-dimethylorsellinic acid is then prenylated
CC by the polyprenyl transferase ausN (PubMed:28233494). Further
CC epoxidation by the FAD-dependent monooxygenase ausM and cyclization by
CC the probable terpene cyclase ausL lead to the formation of
CC protoaustinoid A (By similarity). Protoaustinoid A is then oxidized to
CC spiro-lactone 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:C8VE82, ECO:0000269|PubMed:28233494,
CC ECO:0000269|PubMed:29076725}.
CC -!- PATHWAY: Secondary metabolite biosynthesis; terpenoid biosynthesis.
CC {ECO:0000305|PubMed:28233494}.
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; CDMC01000024; CEL11265.1; -; Genomic_DNA.
DR SMR; A0A0U5GFQ6; -.
DR STRING; 454130.A0A0U5GFQ6; -.
DR EnsemblFungi; CEL11265; CEL11265; ASPCAL14368.
DR OrthoDB; 1471762at2759; -.
DR UniPathway; UPA00213; -.
DR Proteomes; UP000054771; 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_0000453850"
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"
FT BINDING 244
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:Q3J7D1"
SQ SEQUENCE 279 AA; 31966 MW; A187A1382F9D3214 CRC64;
MHPDAQLKAA VKNGFDPNIL CQRRLTVVKE PVRTILEKQG TIPADKIVDH VNELRDRAFA
VFPYACIGQF SFVELSIAES PYYREMLERV KKGDLLLDLG CAFGQELRQL MFDGAPPTNL
YGSDLQQEFL NLGYELFLDQ PIFPESQLIA ADILDKKSAL FVRLQGKLNI VYISLFLHVF
DWDKQVTVLE NVLDLLAATP GSLIVCRVIA CRNQAVLNKT HERMPYYYHD LASWNKLWEE
IRTRTSLRLA VDVWEQPDDL VKKHPLPGIY VLGSAIRRH
