AUSC_PENBI
ID AUSC_PENBI Reviewed; 646 AA.
AC A0A0F7TXA5;
DT 29-SEP-2021, integrated into UniProtKB/Swiss-Prot.
DT 22-JUL-2015, sequence version 1.
DT 03-AUG-2022, entry version 21.
DE RecName: Full=FAD-binding monooxygenase ausC {ECO:0000303|PubMed:29076725};
DE EC=1.14.13.- {ECO:0000305|PubMed:29076725};
DE AltName: Full=Austinoid biosynthesis clusters protein C {ECO:0000303|PubMed:29076725};
GN Name=ausC {ECO:0000303|PubMed:29076725}; ORFNames=PMG11_09855;
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: FAD-binding monooxygenase; part of the gene cluster A that
CC mediates the biosynthesis of the fungal meroterpenoid
CC acetoxydehydroaustin (PubMed:29076725). The first step of the pathway
CC is the synthesis of 3,5-dimethylorsellinic acid by the polyketide
CC synthase ausA (By similarity). 3,5-dimethylorsellinic acid is then
CC prenylated by the polyprenyl transferase ausN (By similarity). 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 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:C8VE79, 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:29076725}.
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; CDHK01000010; CEJ61319.1; -; Genomic_DNA.
DR SMR; A0A0F7TXA5; -.
DR EnsemblFungi; CEJ61319; CEJ61319; PMG11_09855.
DR OrthoDB; 405736at2759; -.
DR UniPathway; UPA00213; -.
DR Proteomes; UP000042958; 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..646
FT /note="FAD-binding monooxygenase ausC"
FT /id="PRO_0000453849"
FT REGION 1..20
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 119..122
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:H3JQW0"
FT BINDING 129..131
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:H3JQW0"
FT BINDING 131..132
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:H3JQW0"
FT BINDING 137
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:H3JQW0"
FT BINDING 275..281
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:H3JQW0"
FT BINDING 298..299
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:H3JQW0"
FT SITE 417
FT /note="Transition state stabilizer"
FT /evidence="ECO:0000250|UniProtKB:H3JQW0"
SQ SEQUENCE 646 AA; 72148 MW; 5C86EBA301CFD8C8 CRC64;
MTISTTTLGS GATTATRKEV EAKYEEERQI QLQSRGMVQD IEITRNASFE QFAKDPWAAP
KQVDVETQRE KLLQQAHHKI VIIGAGFGGL LFAVRLIQTG KFKANDIILV DSAAGFGGTW
YWNRYPGLMC DTESYIYMPL LEETEYMPRN KYASGNEIRE HAERIAEKYN LSERAIFRTV
VQSLDWEEEE KVWKIAGVKL GKDDECQQPF QLMADFAIMA SGAFASPRVP NYPNIFDYKG
KLFHTARWDY KYTGGSIENP KMSGLTNKRV AIIGTGATAI QIVPQLARNS RELFVFQRTP
AAVDVRNNYP TDPARFKSEI QGDGPGWQRR RQINFNAFTC NEKTLPTDNK VGDGWTRMPS
FSVLIGGPQS LEPDYIDEIR PIDMARQSEI RSRVHKLVQS TAIADSLTPW YPGWCKRPCF
HDEYLQSFNS SNVQLVDIRH DGISRFTPKG LVANGVEYEL DAIILSTGYT VPVTRASPSG
RANIAVTGRR GVTMEEKWAN GLATLHGVMT RDLPNLFFAG TSQAGACVNL TYALDQNAIH
VAHILSEAVK RQPSDCTKLV IQPTHEGEEA WTMEILQRAA GFRGIAGCTP GYLNGYGMDA
SSLKPEEQMN MARLAAWGQG IASYVDALEG WRSEGQLEGV EMTFLA
