ID   PSIM_PSICU              Reviewed;         309 AA.
AC   P0DPA9;
DT   25-OCT-2017, integrated into UniProtKB/Swiss-Prot.
DT   25-OCT-2017, sequence version 1.
DT   03-AUG-2022, entry version 15.
DE   RecName: Full=Psilocybin synthase {ECO:0000305};
DE            EC=2.1.1.345 {ECO:0000269|PubMed:28763571};
DE   AltName: Full=Psilocybin biosynthesis methyltransferase {ECO:0000303|PubMed:28763571};
GN   Name=psiM {ECO:0000303|PubMed:28763571};
OS   Psilocybe cubensis (Psychedelic mushroom) (Stropharia cubensis).
OC   Eukaryota; Fungi; Dikarya; Basidiomycota; Agaricomycotina; Agaricomycetes;
OC   Agaricomycetidae; Agaricales; Strophariaceae; Psilocybe.
OX   NCBI_TaxID=181762;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], IDENTIFICATION, FUNCTION, CATALYTIC ACTIVITY,
RP   AND PATHWAY.
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).
CC   -!- FUNCTION: N-methyltransferase; part of the gene cluster that mediates
CC       the biosynthesis of psilocybin, a psychotropic tryptamine-derived
CC       natural product (PubMed:28763571). The first step in the pathway is the
CC       decarboxylation of L-tryptophan to tryptamine by the decarboxylase psiD
CC       (PubMed:28763571). 4-hydroxy-L-tryptophan is accepted as substrate by
CC       psiD as well (PubMed:28763571). The cytochrome P450 monooxygenase psiH
CC       then converts tryptamine to 4-hydroxytryptamine (PubMed:28763571). The
CC       kinase psiK catalyzes the 4-O-phosphorylation step by converting 4-
CC       hydroxytryptamine into norbaeocystin (PubMed:28763571). The
CC       methyltransferase psiM then catalyzes iterative methyl transfer to the
CC       amino group of norbaeocystin to yield psilocybin via a monomethylated
CC       intermediate, baeocystin (PubMed:28763571). PsiK kinase can also turn
CC       psilocin into psilocybin (PubMed:28763571). This activity may represent
CC       a protective mechanism to rephosphorylate the unstable psilocin to the
CC       stable psilocybin in case of intracellular ester cleavage
CC       (PubMed:28763571). {ECO:0000269|PubMed:28763571}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=4-hydoxytryptamine 4-phosphate + 2 S-adenosyl-L-methionine = 2
CC         H(+) + psilocybin + 2 S-adenosyl-L-homocysteine;
CC         Xref=Rhea:RHEA:55568, ChEBI:CHEBI:15378, ChEBI:CHEBI:57856,
CC         ChEBI:CHEBI:59789, ChEBI:CHEBI:139070, ChEBI:CHEBI:139072;
CC         EC=2.1.1.345; Evidence={ECO:0000269|PubMed:28763571};
CC   -!- COFACTOR:
CC       Name=S-adenosyl-L-methionine; Xref=ChEBI:CHEBI:59789;
CC         Evidence={ECO:0000305};
CC   -!- PATHWAY: Secondary metabolite biosynthesis.
CC       {ECO:0000269|PubMed:28763571}.
CC   -!- SIMILARITY: Belongs to the methyltransferase superfamily. METTL16/RlmF
CC       family. {ECO:0000305}.
CC   -!- WEB RESOURCE: Name=Protein Spotlight; Note=When the mind bends - Issue
CC       198 of December 2017;
CC       URL="https://web.expasy.org/spotlight/back_issues/198/";
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; KY984100; ASU62238.1; -; mRNA.
DR   AlphaFoldDB; P0DPA9; -.
DR   SMR; P0DPA9; -.
DR   KEGG; ag:ASU62238; -.
DR   BRENDA; 2.1.1.345; 15552.
DR   GO; GO:0140381; F:4-hydroxytryptamine 4-phosphate methyltransferase activity; IEA:UniProtKB-EC.
DR   GO; GO:0008173; F:RNA methyltransferase activity; IEA:UniProt.
DR   GO; GO:0140380; P:psilocybin biosynthetic process; IDA:GO_Central.
DR   Gene3D; 3.40.50.150; -; 1.
DR   InterPro; IPR017182; METTL16/PsiM.
DR   InterPro; IPR010286; METTL16/RlmF.
DR   InterPro; IPR029063; SAM-dependent_MTases_sf.
DR   PANTHER; PTHR13393; PTHR13393; 1.
DR   Pfam; PF05971; Methyltransf_10; 1.
DR   PIRSF; PIRSF037350; Mtase_ZK1128_prd; 1.
DR   SUPFAM; SSF53335; SSF53335; 1.
PE   1: Evidence at protein level;
KW   Methyltransferase; S-adenosyl-L-methionine; Transferase.
FT   CHAIN           1..309
FT                   /note="Psilocybin synthase"
FT                   /id="PRO_0000442160"
FT   BINDING         75
FT                   /ligand="S-adenosyl-L-methionine"
FT                   /ligand_id="ChEBI:CHEBI:59789"
FT                   /evidence="ECO:0000250|UniProtKB:Q86W50"
FT   BINDING         107
FT                   /ligand="S-adenosyl-L-methionine"
FT                   /ligand_id="ChEBI:CHEBI:59789"
FT                   /evidence="ECO:0000250|UniProtKB:Q86W50"
FT   BINDING         131
FT                   /ligand="S-adenosyl-L-methionine"
FT                   /ligand_id="ChEBI:CHEBI:59789"
FT                   /evidence="ECO:0000250|UniProtKB:Q86W50"
FT   BINDING         183
FT                   /ligand="S-adenosyl-L-methionine"
FT                   /ligand_id="ChEBI:CHEBI:59789"
FT                   /evidence="ECO:0000250|UniProtKB:Q86W50"
SQ   SEQUENCE   309 AA;  34434 MW;  7CAA908D54B6D269 CRC64;
     MHIRNPYRTP IDYQALSEAF PPLKPFVSVN ADGTSSVDLT IPEAQRAFTA ALLHRDFGLT
     MTIPEDRLCP TVPNRLNYVL WIEDIFNYTN KTLGLSDDRP IKGVDIGTGA SAIYPMLACA
     RFKAWSMVGT EVERKCIDTA RLNVVANNLQ DRLSILETSI DGPILVPIFE ATEEYEYEFT
     MCNPPFYDGA ADMQTSDAAK GFGFGVGAPH SGTVIEMSTE GGESAFVAQM VRESLKLRTR
     CRWYTSNLGK LKSLKEIVGL LKELEISNYA INEYVQGSTR RYAVAWSFTD IQLPEELSRP
     SNPELSSLF