AUSC_ASPCI
ID AUSC_ASPCI Reviewed; 670 AA.
AC A0A0U5HAQ4;
DT 29-SEP-2021, integrated into UniProtKB/Swiss-Prot.
DT 16-MAR-2016, sequence version 1.
DT 03-AUG-2022, entry version 16.
DE RecName: Full=FAD-binding monooxygenase ausC {ECO:0000303|PubMed:28233494};
DE EC=1.14.13.- {ECO:0000305|PubMed:28233494};
DE AltName: Full=Austinoid biosynthesis cluster protein C {ECO:0000303|PubMed:28233494};
GN Name=ausC {ECO:0000303|PubMed:28233494}; ORFNames=ASPCAL14371;
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: FAD-binding monooxygenase; part of the gene cluster that
CC mediates the biosynthesis of calidodehydroaustin, a fungal
CC meroterpenoid (PubMed:28233494, PubMed:29076725). The first step of the
CC pathway is the synthesis of 3,5-dimethylorsellinic acid by the
CC polyketide synthase ausA (PubMed:28233494). 3,5-dimethylorsellinic acid
CC is then prenylated by the polyprenyl transferase ausN
CC (PubMed:28233494). Further epoxidation by the FAD-dependent
CC monooxygenase ausM and cyclization by the probable terpene cyclase ausL
CC 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 modifies austinolide to austinol (By similarity).
CC Austinol is further acetylated to austin by the O-acetyltransferase
CC ausP, which spontaneously changes to dehydroaustin (PubMed:28233494).
CC The cytochrome P450 monooxygenase ausR then converts dehydroaustin is
CC into 7-dehydrodehydroaustin (PubMed:28233494). The hydroxylation
CC catalyzed by ausR permits the O-acetyltransferase ausQ to add an
CC additional acetyl group to the molecule, leading to the formation of
CC acetoxydehydroaustin (PubMed:28233494). The short chain dehydrogenase
CC ausT catalyzes the reduction of the double bond present between carbon
CC atoms 1 and 2 to convert 7-dehydrodehydroaustin into 1,2-dihydro-7-
CC hydroxydehydroaustin (PubMed:28233494). AusQ catalyzes not only an
CC acetylation reaction but also the addition of the PKS ausV diketide
CC 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:C8VE79, ECO:0000269|PubMed:28233494,
CC ECO:0000269|PubMed:29076725}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=AH2 + O2 + preaustinoid A = A + H2O + preaustinoid A1;
CC Xref=Rhea:RHEA:65168, ChEBI:CHEBI:13193, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:17499, ChEBI:CHEBI:69023,
CC ChEBI:CHEBI:69026; Evidence={ECO:0000250|UniProtKB:C8VE79};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:65169;
CC Evidence={ECO:0000250|UniProtKB:C8VE79};
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692;
CC Evidence={ECO:0000250|UniProtKB:H3JQW0};
CC Note=Binds 1 FAD per subunit. {ECO:0000250|UniProtKB:H3JQW0};
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}.
CC -!- SIMILARITY: Belongs to the FAD-binding monooxygenase family.
CC {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; CDMC01000024; CEL11268.1; -; Genomic_DNA.
DR SMR; A0A0U5HAQ4; -.
DR EnsemblFungi; CEL11268; CEL11268; ASPCAL14371.
DR OrthoDB; 405736at2759; -.
DR UniPathway; UPA00213; -.
DR Proteomes; UP000054771; Unassembled WGS sequence.
DR GO; GO:0004497; F:monooxygenase activity; IEA:UniProtKB-KW.
DR GO; GO:0016114; P:terpenoid biosynthetic process; IEA:UniProtKB-UniPathway.
DR Gene3D; 3.50.50.60; -; 2.
DR InterPro; IPR036188; FAD/NAD-bd_sf.
DR InterPro; IPR023753; FAD/NAD-binding_dom.
DR Pfam; PF07992; Pyr_redox_2; 1.
DR SUPFAM; SSF51905; SSF51905; 1.
PE 3: Inferred from homology;
KW FAD; Flavoprotein; Monooxygenase; NADP; Oxidoreductase; Reference proteome.
FT CHAIN 1..670
FT /note="FAD-binding monooxygenase ausC"
FT /id="PRO_0000453848"
FT BINDING 144..147
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:H3JQW0"
FT BINDING 154..156
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:H3JQW0"
FT BINDING 156..157
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:H3JQW0"
FT BINDING 162
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:H3JQW0"
FT BINDING 299..305
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:H3JQW0"
FT BINDING 322..323
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:H3JQW0"
FT SITE 441
FT /note="Transition state stabilizer"
FT /evidence="ECO:0000250|UniProtKB:H3JQW0"
SQ SEQUENCE 670 AA; 74225 MW; 99A899CD3884059D CRC64;
MEMRGIENKS DIALAEFRLT GINGPDKDSS GSTYPDAAAV EAKYEAERQI QLRAHETVSD
IEITVDDGWT DLAQDPWAGC PDPAGETPHL LTQRSHLLSQ HRHRVLIVGA GFGGLLFAVR
LLQTGQFKAS DIVIADTAAG FGGTWYWNRY PGLMCDTESY IYMPLLEETG YMPRDKYASG
SEIRQHAERI ARYWGLETRA MFRTSVRDLA WDEDKKIWNV AGRLLGDVMD TEQFRMAADI
VLLASGSFAS PRVPNYPDIA KYKGKLFHTA RWDYQFTGGS LENPKLTGLA DKRVGIIGTG
ASAVQIIPHL ARYSRSLIVF QRTPAAVDAR DNRPTDPVWW KEEMASQGAG WQQRRQKNFN
AFTCNETPLP GNNCVGDGWT RMPSFSLLIG GPQNLAPDYI DQMRAVDLVR QAQIRERAHA
LVQDPVAADL LTPWYPGWCK RPCFHDDYLS ALNEENVRLV DLRHGGLSHF TPSGVVANGE
EYELDLIVLS TGYTVPVTRA SPGSRGNISI TGRNGMTMEA KWANGLATLH GVMTRDLPNL
FFAGTSQAGA CVNLTYSVDQ NATHVAYILG KAFERRPPNC DKVVLQPTHE GEEQWAGEVL
ARAAAFRGIA GCTPGYLNGY GKSLDSLSPE QQVNMARLAA WGEGIASYVN RLEEWREKGE
LEGVEMTFLN
