PSIH_PSICY
ID PSIH_PSICY Reviewed; 507 AA.
AC A0A286LF02;
DT 05-DEC-2018, integrated into UniProtKB/Swiss-Prot.
DT 22-NOV-2017, sequence version 1.
DT 03-AUG-2022, entry version 10.
DE RecName: Full=Tryptamine 4-monooxygenase {ECO:0000303|PubMed:28763571};
DE EC=1.14.99.59 {ECO:0000250|UniProtKB:P0DPA7};
DE AltName: Full=Cytochrome P450 monooxygenase psiH {ECO:0000303|PubMed:28763571};
DE AltName: Full=Psilocybin biosynthesis hydroxylase {ECO:0000303|PubMed:28763571};
DE Flags: Precursor;
GN Name=psiH {ECO:0000303|PubMed:28763571};
OS Psilocybe cyanescens.
OC Eukaryota; Fungi; Dikarya; Basidiomycota; Agaricomycotina; Agaricomycetes;
OC Agaricomycetidae; Agaricales; Strophariaceae; Psilocybe.
OX NCBI_TaxID=93625;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], IDENTIFICATION, FUNCTION, AND PATHWAY.
RC STRAIN=FSU 12416;
RX PubMed=28763571; DOI=10.1002/anie.201705489;
RA Fricke J., Blei F., Hoffmeister D.;
RT "Enzymatic synthesis of psilocybin.";
RL Angew. Chem. Int. Ed. 56:12352-12355(2017).
RN [2]
RP FUNCTION.
RX PubMed=30283667; DOI=10.1002/evl3.42;
RA Reynolds H.T., Vijayakumar V., Gluck-Thaler E., Korotkin H.B.,
RA Matheny P.B., Slot J.C.;
RT "Horizontal gene cluster transfer increased hallucinogenic mushroom
RT diversity.";
RL Evol. Lett. 2:88-101(2018).
CC -!- FUNCTION: Tryptamine 4-monooxygenase; part of the gene cluster that
CC mediates the biosynthesis of psilocybin, a psychotropic tryptamine-
CC derived natural product (PubMed:28763571, PubMed:30283667). The first
CC step in the pathway is the decarboxylation of L-tryptophan to
CC tryptamine by the decarboxylase psiD. PsiD does not decarboxylate
CC phenylalanine, tyrosine, or 5-hydroxy- L -tryptophan (5-HTP)
CC (PubMed:30283667). 4-hydroxy-L-tryptophan is accepted as substrate by
CC psiD as well. The cytochrome P450 monooxygenase psiH then converts
CC tryptamine to 4-hydroxytryptamine. The kinase psiK catalyzes the 4-O-
CC phosphorylation step by converting 4-hydroxytryptamine into
CC norbaeocystin. The methyltransferase psiM then catalyzes iterative
CC methyl transfer to the amino group of norbaeocystin to yield psilocybin
CC via a monomethylated intermediate, baeocystin. PsiK kinase can also
CC turn psilocin into psilocybin. This activity may represent a protective
CC mechanism to rephosphorylate the unstable psilocin to the stable
CC psilocybin in case of intracellular ester cleavage (By similarity).
CC {ECO:0000250|UniProtKB:P0DPA7, ECO:0000269|PubMed:28763571,
CC ECO:0000269|PubMed:30283667}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=AH2 + O2 + tryptamine = 4-hydroxytryptamine + A + H2O;
CC Xref=Rhea:RHEA:15865, ChEBI:CHEBI:13193, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:17499, ChEBI:CHEBI:57887,
CC ChEBI:CHEBI:139069; EC=1.14.99.59;
CC Evidence={ECO:0000250|UniProtKB:P0DPA7};
CC -!- COFACTOR:
CC Name=heme; Xref=ChEBI:CHEBI:30413;
CC Evidence={ECO:0000250|UniProtKB:P04798};
CC -!- PATHWAY: Secondary metabolite biosynthesis.
CC {ECO:0000305|PubMed:28763571}.
CC -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
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DR EMBL; MF000997; ASU62250.1; -; Genomic_DNA.
DR AlphaFoldDB; A0A286LF02; -.
DR SMR; A0A286LF02; -.
DR GO; GO:0020037; F:heme binding; IEA:InterPro.
DR GO; GO:0005506; F:iron ion binding; IEA:InterPro.
DR GO; GO:0016705; F:oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen; IEA:InterPro.
DR GO; GO:0140382; F:tryptamine 4-monooxygenase activity; IEA:UniProtKB-EC.
DR GO; GO:0140380; P:psilocybin biosynthetic process; ISS:GO_Central.
DR Gene3D; 1.10.630.10; -; 1.
DR InterPro; IPR001128; Cyt_P450.
DR InterPro; IPR017972; Cyt_P450_CS.
DR InterPro; IPR002401; Cyt_P450_E_grp-I.
DR InterPro; IPR036396; Cyt_P450_sf.
DR Pfam; PF00067; p450; 1.
DR PRINTS; PR00463; EP450I.
DR PRINTS; PR00385; P450.
DR SUPFAM; SSF48264; SSF48264; 1.
DR PROSITE; PS00086; CYTOCHROME_P450; 1.
PE 2: Evidence at transcript level;
KW Heme; Iron; Metal-binding; Monooxygenase; Oxidoreductase; Signal.
FT SIGNAL 1..19
FT /evidence="ECO:0000255"
FT CHAIN 20..507
FT /note="Tryptamine 4-monooxygenase"
FT /id="PRO_5012470929"
FT REGION 403..425
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 404..425
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
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"
SQ SEQUENCE 507 AA; 57259 MW; BC4356BCB738DF7C CRC64;
MIVLLVSLVL AGCIYYANAR RVRRSRLPPG PPGIPLPFIG NMFDMPSESP WLRFLQWGRD
YHTDILYLNA GGTEIIILNT LDAITDLLEK RGSMYSGRLE STMVNELMGW EFDLGFITYG
ERWREERRMF AKEFSEKNIR QFRHAQIKAA NQLVRQLIKT PDRWSQHIRH QIAAMSLDIG
YGIDLAEDDP WIAATQLANE GLAEASVPGS FWVDSFPALK YLPSWLPGAG FKRKAKVWKE
GADHMVNMPY ETMKKLTVQG LARPSYASAR LQAMDPDGDL EHQEHVIRNT ATEVNVGGGD
TTVSAVSAFI LAMVKYPEVQ RQVQAELDAL TSKGVVPNYD EEDDSLPYLT ACVKEIFRWN
QIAPLAIPHR LIKDDVYRGY LIPKNALVYA NSWAVLNDPE EYPNPSEFRP ERYLSSDGKP
DPTVRDPRKA AFGYGRRNCP GIHLAQSTVW IAGATLLSVF NIERPVDGNG KPIDIPATFT
TGFFRHPEPF QCRFVPRTQE ILKSVSG