CICH_EMENI
ID CICH_EMENI Reviewed; 497 AA.
AC C8V0D4; Q5AZ31;
DT 07-OCT-2020, integrated into UniProtKB/Swiss-Prot.
DT 03-NOV-2009, sequence version 1.
DT 03-AUG-2022, entry version 68.
DE RecName: Full=Cytochrome P450 monooxygenase cicH {ECO:0000303|PubMed:24244835};
DE EC=1.-.-.- {ECO:0000305|PubMed:24244835};
DE AltName: Full=Cichorine biosynthesis cluster protein H {ECO:0000303|PubMed:24244835};
GN Name=cicH {ECO:0000303|PubMed:24244835}; ORFNames=AN6449, ANIA_06449;
OS Emericella nidulans (strain FGSC A4 / ATCC 38163 / CBS 112.46 / NRRL 194 /
OS M139) (Aspergillus nidulans).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Aspergillaceae; Aspergillus;
OC Aspergillus subgen. Nidulantes.
OX NCBI_TaxID=227321;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=FGSC A4 / ATCC 38163 / CBS 112.46 / NRRL 194 / M139;
RX PubMed=16372000; DOI=10.1038/nature04341;
RA Galagan J.E., Calvo S.E., Cuomo C., Ma L.-J., Wortman J.R., Batzoglou S.,
RA Lee S.-I., Bastuerkmen M., Spevak C.C., Clutterbuck J., Kapitonov V.,
RA Jurka J., Scazzocchio C., Farman M.L., Butler J., Purcell S., Harris S.,
RA Braus G.H., Draht O., Busch S., D'Enfert C., Bouchier C., Goldman G.H.,
RA Bell-Pedersen D., Griffiths-Jones S., Doonan J.H., Yu J., Vienken K.,
RA Pain A., Freitag M., Selker E.U., Archer D.B., Penalva M.A., Oakley B.R.,
RA Momany M., Tanaka T., Kumagai T., Asai K., Machida M., Nierman W.C.,
RA Denning D.W., Caddick M.X., Hynes M., Paoletti M., Fischer R., Miller B.L.,
RA Dyer P.S., Sachs M.S., Osmani S.A., Birren B.W.;
RT "Sequencing of Aspergillus nidulans and comparative analysis with A.
RT fumigatus and A. oryzae.";
RL Nature 438:1105-1115(2005).
RN [2]
RP GENOME REANNOTATION.
RC STRAIN=FGSC A4 / ATCC 38163 / CBS 112.46 / NRRL 194 / M139;
RX PubMed=19146970; DOI=10.1016/j.fgb.2008.12.003;
RA Wortman J.R., Gilsenan J.M., Joardar V., Deegan J., Clutterbuck J.,
RA Andersen M.R., Archer D., Bencina M., Braus G., Coutinho P., von Dohren H.,
RA Doonan J., Driessen A.J., Durek P., Espeso E., Fekete E., Flipphi M.,
RA Estrada C.G., Geysens S., Goldman G., de Groot P.W., Hansen K.,
RA Harris S.D., Heinekamp T., Helmstaedt K., Henrissat B., Hofmann G.,
RA Homan T., Horio T., Horiuchi H., James S., Jones M., Karaffa L.,
RA Karanyi Z., Kato M., Keller N., Kelly D.E., Kiel J.A., Kim J.M.,
RA van der Klei I.J., Klis F.M., Kovalchuk A., Krasevec N., Kubicek C.P.,
RA Liu B., Maccabe A., Meyer V., Mirabito P., Miskei M., Mos M., Mullins J.,
RA Nelson D.R., Nielsen J., Oakley B.R., Osmani S.A., Pakula T., Paszewski A.,
RA Paulsen I., Pilsyk S., Pocsi I., Punt P.J., Ram A.F., Ren Q., Robellet X.,
RA Robson G., Seiboth B., van Solingen P., Specht T., Sun J.,
RA Taheri-Talesh N., Takeshita N., Ussery D., vanKuyk P.A., Visser H.,
RA van de Vondervoort P.J., de Vries R.P., Walton J., Xiang X., Xiong Y.,
RA Zeng A.P., Brandt B.W., Cornell M.J., van den Hondel C.A., Visser J.,
RA Oliver S.G., Turner G.;
RT "The 2008 update of the Aspergillus nidulans genome annotation: a community
RT effort.";
RL Fungal Genet. Biol. 46:S2-13(2009).
RN [3]
RP FUNCTION.
RX PubMed=22510154; DOI=10.1021/ja3016395;
RA Ahuja M., Chiang Y.M., Chang S.L., Praseuth M.B., Entwistle R.,
RA Sanchez J.F., Lo H.C., Yeh H.H., Oakley B.R., Wang C.C.;
RT "Illuminating the diversity of aromatic polyketide synthases in Aspergillus
RT nidulans.";
RL J. Am. Chem. Soc. 134:8212-8221(2012).
RN [4]
RP FUNCTION, DISRUPTION PHENOTYPE, AND PATHWAY.
RX PubMed=24244835; DOI=10.1039/c2md20055d;
RA Sanchez J.F., Entwistle R., Corcoran D., Oakley B.R., Wang C.C.;
RT "Identification and molecular genetic analysis of the cichorine gene
RT cluster in Aspergillus nidulans.";
RL Med. Chem. Commun. 3:0-0(2012).
RN [5]
RP BIOTECHNOLOGY.
RX PubMed=30708999; DOI=10.3390/molecules24030515;
RA Liao L., Zhang X., Lou Y., Zhou C., Yuan Q., Gao J.;
RT "Discovery of three new phytotoxins from the fungus Aspergillus nidulans by
RT pathway inactivation.";
RL Molecules 24:0-0(2019).
CC -!- FUNCTION: Cytochrome P450 monooxygenase; part of the gene cluster that
CC mediates the biosynthesis of cichorine, a phytotoxin active against
CC knapweed, corn, and soybeans (PubMed:24244835). The first step in the
CC pathway is performed by the non-reducing polyketide synthase pkbA that
CC condenses one acetyl-CoA starter unit with 3 malonyl-CoA units
CC (PubMed:22510154). PkbA also catalyzes one methylation step to produce
CC 3-methylorsellinate (PubMed:22510154). The nonribosomal peptide
CC synthase-like protein cicB, the cytochrome P450 monooxygenase cicH and
CC the O-methyltransferase cicE are involved in the conversion of 3-
CC methylorsellinate into nidulol (PubMed:24244835). CicB converts 3-
CC methylorsellinate to a yet unidentified intermediate, cicH may play a
CC ring-closing role for cichorine and cicE is plausibly responsible for
CC the methylation of one of the phenol groups (Probable). The
CC oxidoreductase cicC acts downstream with still unidentified enzymes to
CC further convert nidulol into cichorine (PubMed:24244835).
CC {ECO:0000269|PubMed:22510154, ECO:0000269|PubMed:24244835,
CC ECO:0000305|PubMed:24244835}.
CC -!- COFACTOR:
CC Name=heme; Xref=ChEBI:CHEBI:30413;
CC Evidence={ECO:0000250|UniProtKB:P04798};
CC -!- PATHWAY: Phytotoxin biosynthesis. {ECO:0000269|PubMed:24244835}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000255}; Single-pass membrane
CC protein {ECO:0000255}.
CC -!- DISRUPTION PHENOTYPE: Abolishes the production of cichorine.
CC {ECO:0000269|PubMed:24244835}.
CC -!- BIOTECHNOLOGY: Cichorine and its derivatives are promising in the
CC course of developing novel herbicides. {ECO:0000269|PubMed:30708999}.
CC -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=EAA58471.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
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DR EMBL; AACD01000108; EAA58471.1; ALT_SEQ; Genomic_DNA.
DR EMBL; BN001301; CBF69449.1; -; Genomic_DNA.
DR RefSeq; XP_664053.1; XM_658961.1.
DR AlphaFoldDB; C8V0D4; -.
DR SMR; C8V0D4; -.
DR EnsemblFungi; CBF69449; CBF69449; ANIA_06449.
DR EnsemblFungi; EAA58471; EAA58471; AN6449.2.
DR GeneID; 2871345; -.
DR KEGG; ani:AN6449.2; -.
DR VEuPathDB; FungiDB:AN6449; -.
DR eggNOG; KOG0159; Eukaryota.
DR HOGENOM; CLU_001570_14_0_1; -.
DR InParanoid; C8V0D4; -.
DR OMA; MEVEAND; -.
DR OrthoDB; 467733at2759; -.
DR Proteomes; UP000000560; Chromosome I.
DR Proteomes; UP000005890; Unassembled WGS sequence.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0020037; F:heme binding; IEA:InterPro.
DR GO; GO:0005506; F:iron ion binding; IEA:InterPro.
DR GO; GO:0004497; F:monooxygenase activity; IEA:UniProtKB-KW.
DR GO; GO:0016705; F:oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen; IEA:InterPro.
DR GO; GO:0062032; P:cichorine biosynthetic process; IMP:GO_Central.
DR GO; GO:0044550; P:secondary metabolite biosynthetic process; IMP:AspGD.
DR Gene3D; 1.10.630.10; -; 1.
DR InterPro; IPR001128; Cyt_P450.
DR InterPro; IPR017972; Cyt_P450_CS.
DR InterPro; IPR002403; Cyt_P450_E_grp-IV.
DR InterPro; IPR036396; Cyt_P450_sf.
DR Pfam; PF00067; p450; 1.
DR PRINTS; PR00465; EP450IV.
DR PRINTS; PR00385; P450.
DR SUPFAM; SSF48264; SSF48264; 1.
DR PROSITE; PS00086; CYTOCHROME_P450; 1.
PE 1: Evidence at protein level;
KW Glycoprotein; Heme; Iron; Membrane; Metal-binding; Monooxygenase;
KW Oxidoreductase; Reference proteome; Transmembrane; Transmembrane helix.
FT CHAIN 1..497
FT /note="Cytochrome P450 monooxygenase cicH"
FT /id="PRO_0000450887"
FT TRANSMEM 2..19
FT /note="Helical"
FT /evidence="ECO:0000255"
FT BINDING 439
FT /ligand="heme"
FT /ligand_id="ChEBI:CHEBI:30413"
FT /ligand_part="Fe"
FT /ligand_part_id="ChEBI:CHEBI:18248"
FT /note="axial binding residue"
FT /evidence="ECO:0000250|UniProtKB:P04798"
FT CARBOHYD 443
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ SEQUENCE 497 AA; 56706 MW; 1077BE976C90A2A9 CRC64;
MAILVRLFFA LFVVSVYFFR VRLRLSHIPG PFLASLTNIN RRQWVTTGRA HTIHTELHRQ
YGKVVRAGPN TVFVSDPAAI PAIYRFNEPY QKSEFYDALM PYVRGKSIPD VFATRDEHIH
RTMKQPIAAI YSMSNLVSFE PYVKSTIEYF FSRLDSLFVE TGKVCNFGLW LHLFASDVMG
EITFSRRLGF LETGGDMENV MANNWKFFVQ AAPATQMPWL DYFWKRNPLL PGSVKPNKVI
EFGVARIQER LHLSEKHPDH VNSRDFLSRF IAAKEKNSQI GPDAIMTWAN SNIQAGSDTT
AILLSALFYH LLKNPTSLAA LCTEIDAAAK RGCLSSILTW KETRDLPYLD ACVKEAARLH
PPISLPLERV IPESGTVIGG FKIPGGTRVA MNPWAVHRDR DVFGADADTW RPERWLEGEE
KAKTLYNSLL TFGGGHRSCL GKNISYLEIY KLVPSILLRY EIGLAEPEKE WHLENRWFVM
PSRFYVRLKA RNGVTKL