Editing Psilocybin (section)

===Biosynthesis===
[[Isotopic labeling]] experiments from the 1960s suggested that the [[biosynthesis]] of psilocybin was a four-step process:<ref name="Agurell1968" />

# [[Decarboxylation]] of [[tryptophan]] to [[tryptamine]]
# ''N'',''N''-Dimethylation of tryptamine at the N<sup>9</sup> position to [[dimethyltryptamine]]
# 4-[[Hydroxylation]] of dimethyltryptamine to [[psilocin]]
# ''O''-[[Phosphorylation]] of psilocin to psilocybin

This process can be seen in the following diagram:<ref name=Fricke2017/>

[[File:Biosynthesis of psilocybin.svg|class=skin-invert-image|thumb|upright=2.5|center|Biosynthetic route previously thought to lead to psilocybin. It has recently been shown that 4-hydroxylation and O-phosphorylation immediately follow decarboxylation, and neither dimethyltryptamine nor psilocin are intermediates, although spontaneously generated psilocin can be converted back to psilocybin.<ref name=Fricke2017/>]]{{clear left}}

More recent research has demonstrated that—at least in ''P. cubensis''—''O''-phosphorylation is in fact the third step, and that neither dimethyltryptamine nor psilocin are intermediates.<ref name=Fricke2017/> The sequence of the intermediate steps has been shown to involve four enzymes (PsiD, PsiH, PsiK, and PsiM) in ''P. cubensis'' and ''P. cyanescens'', although it is possible that the biosynthetic pathway differs between species.<ref name = Wurst2002 />{{rp|12–13}}<ref name=Fricke2017/> These enzymes are encoded in [[Metabolic gene cluster|gene clusters]] in ''Psilocybe, Panaeolus,'' and ''Gymnopilus''.<ref name=Reynolds2018/>

''[[Escherichia coli]]'' has been genetically modified to manufacture large amounts of psilocybin.<ref>{{Cite journal |vauthors=Satyanarayana M |date=7 October 2019 |title=Modified ''E. coli'' pump out psilocybin |url=https://cen.acs.org/biological-chemistry/biotechnology/Modified-E-coli-pump-magic/97/i39 |url-status=live |journal=[[Chemical & Engineering News]] |volume=97 |issue=39 |page=11 |doi=10.1021/cen-09739-scicon9 |archive-url=https://web.archive.org/web/20191203042315/https://cen.acs.org/biological-chemistry/biotechnology/Modified-E-coli-pump-magic/97/i39 |archive-date=December 3, 2019 |access-date=December 3, 2019 |s2cid=208747979}}</ref> Psilocybin can be produced ''de novo'' in GM yeast.<ref name=Milne2020/><ref name=Wong2022/>