ID   PSIM_PSICY              Reviewed;         309 AA.
AC   A0A286LEZ7;
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=Psilocybin synthase {ECO:0000305};
DE            EC=2.1.1.345 {ECO:0000250|UniProtKB:P0DPA9};
DE   AltName: Full=Psilocybin biosynthesis methyltransferase {ECO:0000303|PubMed:28763571};
GN   Name=psiM {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: Methyltransferase; part of the gene cluster that mediates the
CC       biosynthesis of psilocybin, a psychotropic tryptamine-derived natural
CC       product (PubMed:28763571, PubMed:30283667). The first step in the
CC       pathway is the decarboxylation of L-tryptophan to tryptamine by the
CC       decarboxylase psiD. PsiD does not decarboxylate phenylalanine,
CC       tyrosine, or 5-hydroxy- L -tryptophan (5-HTP) (PubMed:30283667). 4-
CC       hydroxy-L-tryptophan is accepted as substrate by psiD as well. The
CC       cytochrome P450 monooxygenase psiH then converts tryptamine to 4-
CC       hydroxytryptamine. The kinase psiK catalyzes the 4-O-phosphorylation
CC       step by converting 4-hydroxytryptamine into norbaeocystin. 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. PsiK kinase can also turn psilocin into
CC       psilocybin. This activity may represent a protective mechanism to
CC       rephosphorylate the unstable psilocin to the stable psilocybin in case
CC       of intracellular ester cleavage (By similarity).
CC       {ECO:0000250|UniProtKB:P0DPA9, ECO:0000269|PubMed:28763571,
CC       ECO:0000269|PubMed:30283667}.
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:0000250|UniProtKB:P0DPA9};
CC   -!- COFACTOR:
CC       Name=S-adenosyl-L-methionine; Xref=ChEBI:CHEBI:59789;
CC         Evidence={ECO:0000305};
CC   -!- PATHWAY: Secondary metabolite biosynthesis.
CC       {ECO:0000305|PubMed:28763571}.
CC   -!- SIMILARITY: Belongs to the methyltransferase superfamily. METTL16/RlmF
CC       family. {ECO:0000305}.
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DR   EMBL; KY984103; ASU62241.1; -; mRNA.
DR   AlphaFoldDB; A0A286LEZ7; -.
DR   SMR; A0A286LEZ7; -.
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; ISS: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   2: Evidence at transcript level;
KW   Methyltransferase; S-adenosyl-L-methionine; Transferase.
FT   CHAIN           1..309
FT                   /note="Psilocybin synthase"
FT                   /id="PRO_0000445829"
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;  34312 MW;  D366DDC0B2D0F8F7 CRC64;
     MHIRNPYRDG VDYQALAEAF PALKPHVTVN SDNTTSIDFA VPEAQRLYTA ALLHRDFGLT
     ITLPEDRLCP TVPNRLNYVL WVEDILKVTS DALGLPDNRQ VKGIDIGTGA SAIYPMLACS
     RFKTWSMVAT EVDQKCIDTA RLNVIANNLQ ERLAIIATSV DGPILVPLLQ ANSDFEYDFT
     MCNPPFYDGA SDMQTSDAAK GFGFGVNAPH TGTVLEMATE GGESAFVAQM VRESLNLQTR
     CRWFTSNLGK LKSLYEIVGL LREHQISNYA INEYVQGATR RYAIAWSFID VRLPDHLSRP
     SNPDLSSLF