ID   CNSC_PENEN              Reviewed;         495 AA.
AC   A0A0A2JY25;
DT   10-APR-2019, integrated into UniProtKB/Swiss-Prot.
DT   04-FEB-2015, sequence version 1.
DT   03-AUG-2022, entry version 24.
DE   RecName: Full=Cytochrome P450 monooxygenase cnsC {ECO:0000303|PubMed:25571861};
DE            EC=1.-.-.- {ECO:0000269|PubMed:26963294};
DE   AltName: Full=Communesin biosynthesis cluster protein C {ECO:0000303|PubMed:25571861};
GN   Name=cnsC {ECO:0000303|PubMed:25571861}; ORFNames=PEX2_055370;
OS   Penicillium expansum (Blue mold rot fungus).
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC   Eurotiomycetidae; Eurotiales; Aspergillaceae; Penicillium.
OX   NCBI_TaxID=27334;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=MD-8;
RX   PubMed=25338147; DOI=10.1094/MPMI-09-14-0261-FI;
RA   Ballester A.R., Marcet-Houben M., Levin E., Sela N., Selma-Lazaro C.,
RA   Carmona L., Wisniewski M., Droby S., Gonzalez-Candelas L., Gabaldon T.;
RT   "Genome, transcriptome, and functional analyses of Penicillium expansum
RT   provide new insights into secondary metabolism and pathogenicity.";
RL   Mol. Plant Microbe Interact. 28:232-248(2015).
RN   [2]
RP   IDENTIFICATION, FUNCTION, DISRUPTION PHENOTYPE, AND PATHWAY.
RX   PubMed=25571861; DOI=10.1002/anie.201411297;
RA   Lin H.C., Chiou G., Chooi Y.H., McMahon T.C., Xu W., Garg N.K., Tang Y.;
RT   "Elucidation of the concise biosynthetic pathway of the communesin indole
RT   alkaloids.";
RL   Angew. Chem. Int. Ed. 54:3004-3007(2015).
RN   [3]
RP   FUNCTION, CATALYTIC ACTIVITY, AND PATHWAY.
RX   PubMed=26963294; DOI=10.1021/jacs.6b01413;
RA   Lin H.C., McMahon T.C., Patel A., Corsello M., Simon A., Xu W., Zhao M.,
RA   Houk K.N., Garg N.K., Tang Y.;
RT   "P450-mediated coupling of indole fragments to forge communesin and
RT   unnatural isomers.";
RL   J. Am. Chem. Soc. 138:4002-4005(2016).
CC   -!- FUNCTION: Cytochrome P450 monooxygenase; part of the gene cluster that
CC       mediates the biosynthesis of communesins, a prominent class of indole
CC       alkaloids with great potential as pharmaceuticals (PubMed:25571861).
CC       Communesins are biosynthesized by the coupling of tryptamine and
CC       aurantioclavine, two building blocks derived from L-tryptophan
CC       (PubMed:25571861). The L-tryptophan decarboxylase cnsB converts L-
CC       tryptophan to tryptamine, whereas the tryptophan
CC       dimethylallyltransferase cnsF converts L-tryptophan to 4-dimethylallyl
CC       tryptophan which is further transformed to aurantioclavine by the
CC       aurantioclavine synthase cnsA, probably aided by the catalase cnsD
CC       (PubMed:25571861). The cytochrome P450 monooxygenase cnsC catalyzes the
CC       heterodimeric coupling between the two different indole moieties,
CC       tryptamine and aurantioclavine, to construct vicinal quaternary
CC       stereocenters and yield the heptacyclic communesin scaffold
CC       (PubMed:26963294). The O-methyltransferase cnsE then methylates the
CC       communesin scaffold to produce communesin K, the simplest characterized
CC       communesin that contains the heptacyclic core (PubMed:25571861). The
CC       dioxygenase cnsJ converts communesin K into communesin I
CC       (PubMed:25571861). Acylation to introduce the hexadienyl group at
CC       position N16 of communesin I by the acyltransferase cnsK leads to the
CC       production of communesin B. The hexadienyl group is produced by the
CC       highly reducing polyketide synthase cnsI, before being hydrolytically
CC       removed from cnsI by the serine hydrolase cnsH, converted into
CC       hexadienyl-CoA by the CoA ligase cnsG, and then transferred to
CC       communesin I by cnsK (PubMed:25571861). Surprisingly, cnsK may also be
CC       a promiscuous acyltransferase that can tolerate a range of acyl groups,
CC       including acetyl-, propionyl-, and butyryl-CoA, which lead to
CC       communesins A, G and H respectively (PubMed:25571861). The roles of the
CC       alpha-ketoglutarate-dependent dioxygenases cnsM and cnsP have still to
CC       be determined (PubMed:25571861). {ECO:0000269|PubMed:25571861,
CC       ECO:0000269|PubMed:26963294}.
CC   -!- COFACTOR:
CC       Name=heme; Xref=ChEBI:CHEBI:30413;
CC         Evidence={ECO:0000250|UniProtKB:P04798};
CC   -!- PATHWAY: Alkaloid biosynthesis. {ECO:0000269|PubMed:25571861}.
CC   -!- DISRUPTION PHENOTYPE: Abolishes the biosynthesis of communesins A and B
CC       and leads to the accumulation of aurantioclavine.
CC       {ECO:0000269|PubMed:25571861}.
CC   -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
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DR   EMBL; JQFZ01000090; KGO59696.1; -; Genomic_DNA.
DR   RefSeq; XP_016600809.1; XM_016742811.1.
DR   AlphaFoldDB; A0A0A2JY25; -.
DR   SMR; A0A0A2JY25; -.
DR   EnsemblFungi; KGO59696; KGO59696; PEX2_055370.
DR   GeneID; 27678230; -.
DR   HOGENOM; CLU_022195_8_0_1; -.
DR   OrthoDB; 614788at2759; -.
DR   Proteomes; UP000030143; Unassembled WGS sequence.
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:0008152; P:metabolic process; IEA:UniProt.
DR   Gene3D; 1.10.630.10; -; 1.
DR   InterPro; IPR001128; Cyt_P450.
DR   InterPro; IPR002403; Cyt_P450_E_grp-IV.
DR   InterPro; IPR036396; Cyt_P450_sf.
DR   Pfam; PF00067; p450; 1.
DR   PRINTS; PR00465; EP450IV.
DR   SUPFAM; SSF48264; SSF48264; 1.
PE   1: Evidence at protein level;
KW   Heme; Iron; Metal-binding; Monooxygenase; NADP; Oxidoreductase;
KW   Reference proteome.
FT   CHAIN           1..495
FT                   /note="Cytochrome P450 monooxygenase cnsC"
FT                   /id="PRO_0000446454"
FT   BINDING         434
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"
SQ   SEQUENCE   495 AA;  56193 MW;  880465442C25A7F5 CRC64;
     MKLAPAFPRS YFMGRFWAGN TTGDGLEQTW LDGYYRYTKR GKVFARKTEL NNWSLIFPSE
     LSHDWRNLPL DQISFQHWAQ EGGKIKHHTV LTKAHSKVAL LFAKKELLLA VQKILVKETL
     SLLPGIIGDK WVSLDLMQVC SDLVIKLNAR ILYGPAYADD QDFHKRLITF ANGVDGINSI
     YFTWPRSLWK IVSLVHPTIR GFYANLPHLK KRMLPDIRSR IAKLQAKAAQ GEGKVPASDE
     DVTFMTALIK MHMEEGTLGE QDSDLEKVCM EAVFYTYEFW GPIMPTLFFM LMAIGKNPGY
     LQALREEISS ALESNDWSSD FLARTPKLES FIREVLRLYV PAQWLITDIH RASLATVSRR
     TEKPIYVQSM DMHIPAGVNL CVPAKYIHRD PDFYPNPTTF DGFRFYDPVT NNVTIRATTA
     TDTYLSFSHG SGLCPGRVFG AHVVQVLCAV FIMEYDVKVD PSKTFPDVQS TKEGRGDGMV
     GTTDILIRKR TSAKV