CPAO_ASPOZ
ID CPAO_ASPOZ Reviewed; 455 AA.
AC F5HN72;
DT 29-OCT-2014, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 1.
DT 03-AUG-2022, entry version 31.
DE RecName: Full=Beta-cyclopiazonate dehydrogenase {ECO:0000305};
DE EC=1.21.99.1 {ECO:0000303|PubMed:21608094};
DE AltName: Full=Beta-Cyclopiazonate oxidocyclase {ECO:0000303|PubMed:21608094};
DE AltName: Full=FAD-dependent oxidoreductase cpaO {ECO:0000305};
DE Flags: Precursor;
GN Name=cpaO {ECO:0000303|PubMed:21608094};
OS Aspergillus oryzae (Yellow koji mold).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Aspergillaceae; Aspergillus;
OC Aspergillus subgen. Circumdati.
OX NCBI_TaxID=5062;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, DISRUPTION PHENOTYPE, AND
RP CATALYTIC ACTIVITY.
RC STRAIN=NBRC 4177;
RX PubMed=21608094; DOI=10.1002/cbic.201000672;
RA Kato N., Tokuoka M., Shinohara Y., Kawatani M., Uramoto M., Seshime Y.,
RA Fujii I., Kitamoto K., Takahashi T., Takahashi S., Koyama Y., Osada H.;
RT "Genetic safeguard against mycotoxin cyclopiazonic acid production in
RT Aspergillus oryzae.";
RL ChemBioChem 12:1376-1382(2011).
RN [2]
RP FUNCTION, CATALYTIC ACTIVITY, AND DOMAIN.
RX PubMed=19663400; DOI=10.1021/bi901123r;
RA Liu X., Walsh C.T.;
RT "Cyclopiazonic acid biosynthesis in Aspergillus sp.: characterization of a
RT reductase-like R* domain in cyclopiazonate synthetase that forms and
RT releases cyclo-acetoacetyl-L-tryptophan.";
RL Biochemistry 48:8746-8757(2009).
RN [3]
RP FUNCTION.
RX PubMed=19877600; DOI=10.1021/bi901597j;
RA Liu X., Walsh C.T.;
RT "Characterization of cyclo-acetoacetyl-L-tryptophan
RT dimethylallyltransferase in cyclopiazonic acid biosynthesis: substrate
RT promiscuity and site directed mutagenesis studies.";
RL Biochemistry 48:11032-11044(2009).
CC -!- FUNCTION: Beta-cyclopiazonate dehydrogenase; part of the gene cluster
CC that mediates the biosynthesis of the fungal neurotoxin cyclopiazonic
CC acid (CPA), a nanomolar inhibitor of Ca(2+)-ATPase with a unique
CC pentacyclic indole tetramic acid scaffold (PubMed:21608094). The hybrid
CC two module polyketide synthase-nonribosomal peptide synthetase (PKS-
CC NRPS) cpaS incorporates acetyl-CoA, malonyl-CoA, and tryptophan (Trp)
CC and utilizes a C-terminal redox-incompetent reductase domain to make
CC and release the tryptophan tetramic acid, cyclo-acetoacetyl-L-
CC tryptophan (c-AATrp), as the first intermediate in the pathway. CpaS
CC catalyzes a Dieckmann-type cyclization on the N-acetoacetyl-Trp
CC intermediate bound in thioester linkage to the phosphopantetheinyl arm
CC of the T domain to form and release c-AATrp (PubMed:19663400). CpaD
CC than regiospecifically dimethylallylates c-AATrp to form beta-
CC cyclopiazonic acid. CpaD discriminates against free Trp but accepts
CC tryptophan-containing thiohydantoins, diketopiperazines, and linear
CC peptides as substrates for C4-prenylation and also acts as
CC regiospecific O-dimethylallyltransferase (DMAT) on a tyrosine-derived
CC tetramic acid (PubMed:21608094, PubMed:19877600). The beta-
CC cyclopiazonate dehydrogenase cpaO then carries out the dehydrogenation
CC of beta-CPA to yield an unstable enimine product, which is captured by
CC intramolecular cyclization to create the pentacyclic fused scaffold of
CC alpha-cyclopiazonate (PubMed:21608094). Fimally, the cytochrome P450
CC monooxygenase cpaH mediates the conversion of CPA into the less toxic
CC 2-oxocyclopiazonic acid, the end product of the CPA pathway in A.oryza
CC (PubMed:21608094). {ECO:0000269|PubMed:19663400,
CC ECO:0000269|PubMed:19877600, ECO:0000269|PubMed:21608094}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=A + beta-cyclopiazonate = AH2 + alpha-cyclopiazonate;
CC Xref=Rhea:RHEA:14525, ChEBI:CHEBI:13193, ChEBI:CHEBI:17499,
CC ChEBI:CHEBI:58067, ChEBI:CHEBI:58256; EC=1.21.99.1;
CC Evidence={ECO:0000303|PubMed:21608094};
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692;
CC Evidence={ECO:0000250|UniProtKB:B8NI10};
CC -!- DISRUPTION PHENOTYPE: Impairs the production of cyclopiazonic acid, but
CC accumulates its biosynthetic intermediates cyclo-acetoacetyl-L-
CC tryptophan and beta-cyclopiazonic acid. {ECO:0000269|PubMed:21608094}.
CC -!- SIMILARITY: Belongs to the beta-cyclopiazonate dehydrogenase 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; AB506492; BAK26560.1; -; Genomic_DNA.
DR AlphaFoldDB; F5HN72; -.
DR SMR; F5HN72; -.
DR EnsemblFungi; BAE59504; BAE59504; AO090026000003.
DR VEuPathDB; FungiDB:AO090026000003; -.
DR eggNOG; ENOG502R1TU; Eukaryota.
DR OMA; WASDYST; -.
DR BioCyc; MetaCyc:MON-18888; -.
DR GO; GO:0050448; F:beta-cyclopiazonate dehydrogenase activity; IEA:UniProtKB-EC.
DR Gene3D; 3.50.50.60; -; 1.
DR InterPro; IPR036188; FAD/NAD-bd_sf.
DR SUPFAM; SSF51905; SSF51905; 1.
PE 1: Evidence at protein level;
KW FAD; Flavoprotein; Oxidoreductase; Signal; Virulence.
FT SIGNAL 1..25
FT /evidence="ECO:0000255"
FT CHAIN 26..455
FT /note="Beta-cyclopiazonate dehydrogenase"
FT /id="PRO_0000430691"
SQ SEQUENCE 455 AA; 50983 MW; 387A45ECE71D7A72 CRC64;
MAVRIARFLG LSTVAYLALA NGIDARDTIS RDVIILGGGS SGTYAAIRLR DQGKTVAVVE
RNNYLGGHGE TYYTEDNTPL NFGVEGFFNT TVTRNYLERL QVPYGRRDPA PAHEDYVNLN
TGQRTEYTPG QLQDREAFAK WVDAISQFGF LDDGVYRIPE PVPEDLISPF ADFVKKYHLE
DAVYALFSHT SGDVLEMITL YVIQYIGVPH AAALNEGYVR PIEGIAALYK SAGKELGSDV
LLETTPEAVQ RFEDGVEVIV RSADGTKTLL KGKQLLVTIP PLLENLHGFP LSDQESRLFS
KWQYHQYWAA LVNDTGLPDD VNIVNVDTER LYGVPEEPFI WRLDNHWAPG YHNIKLVGGS
EFGEDEAKAY MYERLDLLHA EGTYATHKPE IVKFASHTPV TMFVSAEEIR GGFYRQLYEL
QGLNSTFWTG ATWASDYSTL LWGYTDEVLD QMASS
