Genetic engineering of fungi to modulate tryptamine expression

A method of treating a depression or an anxiety in a subject, the method comprising:

• administering to the subject an effective amount of a pharmaceutical composition comprising:
• a genetically modified psilocybe fungus, comprising a genetic modification in at least one psilocybin biosynthesis gene selected from:
• a PsiD gene, a PsiH, gene, a PsiM, gene, a PsiK gene, or a combination thereof, wherein the genetic modification results in an increased amount of a compound selected from:
• or derivatives or analogs thereof, compared to production of the same compound in a comparable control psilocybe fungus without the genetic modification,
• wherein:
• the genetic modification comprises an insertion of a polynucleotide encoding the at least one psilocybin biosynthesis gene into a genome of the genetically modified psilocybe fungus, a substitution of at least one nucleobase in a psilocybin biosynthesis gene sequence in the genome of the genetically modified psilocybe fungus, or a combination thereof,
• the genetic modification results in an increased expression of the at least one psilocybin biosynthesis gene compared to the expression of the at least one psilocybin biosynthesis gene in a comparable control psilocybe fungus without the genetic modification;
• and
• the genetically modified psilocybe fungus comprises at least 200% more of the compound measured by dry weight of the fungus compared to the amount of the compound in a comparable control psilocybe fungus without the genetic modification,
• thereby treating the depression or the anxiety in the subject.