US 2024/0254533 A1 · METHODS FOR PRODUCING TRYPTAMINE DERIVATIVES

Abstract

The present disclosure relate to a method for producing a tryptamine derivative of formula (I), wherein the tryptamine derivative (I) is not tryptophane, 4-hydroxytryptamine, N-acetyl-4-hydroxytryptamine, norbaeocystin, baeocystin; psilocybin, psilocin, aeruginascin, halogenated tryptophan, halogenated tryptamine, halogenated N-methylated tryptamine, halogenated N,N-dimethyltryptamine or halogenated N,N,N-trimethyltryptamine; said method comprising providing an indole acceptor of the formula (II), wherein the tryptamine derivative (I) is not tryptophane, 4-hydroxytryptamine, N-acetyl-4-hydroxytryptamine, norbaeocystin, baeocystin; psilocybin, psilocin, aeruginascin, halogenated tryptophan, halogenated tryptamine, halogenated N-methylated tryptamine, halogenated N,N-dimethyltryptamine or halogenated N,N,N-trimethyltryptamine; said method comprising providing an indole acceptor of the formula (II), wherein one or more of RII, RIV, RV, RVI or RVII is not H and Rill is H or CH2CH2NH2 or CH2CHCOOHNH2; and contacting the indole acceptor with a substituent donor in the presence of one or more enzymes substituting one or more H, OH and/or COOH in the indole acceptor with one or more substituents of the substituent donor.

Claims159

Dependent claims

A method for producing a tryptamine derivative of formula (I):

wherein the tryptamine derivative (I) is not tryptophane, 4-hydroxytryptamine, N-acetyl-4-hydroxytryptamine, norbaeocystin, baeocystin;
psilocybin, psilocin, aeruginascin, halogenated tryptophan, halogenated tryptamine, halogenated N-methylated tryptamine, halogenated N,N-dimethyltryptamine or halogenated N,N,N-trimethyltryptamine;
said method comprising providing an indole acceptor of the formula (II):
wherein one or more of RII, RIV, RV, RVI or RVII is not H and RIII is H or CH2CH2NH2 or CH2CHCOOHNH2;
and contacting the indole acceptor with a substituent donor in the presence of one or more enzymes substituting one or more H, OH and/or COOH in the indole acceptor with one or more substituents of the substituent donor.

2 more elements

The method of any preceding claim, wherein the alkyl group is an ethyl or a methyl group.

The method of any preceding claim comprising in vitro enzymatic substitution steps and/or optionally in vivo enzymatic substitution steps.

A tryptamine derivative of formula (I):

wherein at least one of R2, R4 to R9, α and β is a glycosyl group.

A genetically modified microbial host cell producing a serotonin indole acceptor expressing

a) one or more genes encoding polypeptides selected from
i. one or more enzymes converting glucose to fructose-6-phosphate;
ii. a fructose-6-phosphate phosphoketolase converting fructose-6-phosphate to Erythrose-4-phosphate and acetyl phosphate;
iii. a Phosphotransacetylase converting Acetyl phosphate to Acetyl-CoA;
iv. one or more enzymes converting Fructose-6-phosphate to Phosphoenolpyruvate;
v. a 3-deoxy-D-arabino-heptulosonate 7-phosphate synthase (DAHP synthase) converting Phosphoenolpyruvate and Erythrose-4-phosphate to 3-deoxy-D-arabino-heptulosonate-7-phosphate (DAHP);
vi. one or more enzymes converting 3-deoxy-D-arabino-heptulosonate-7-phosphate to 5-enolpyruvoyl-shikimate 3-phosphate;
vii. a Shikimate kinase converting Shikimate to Shikimate-3-phosphate;
viii. a Chorismate synthase converting 5-enolpyruvoyl-shikimate 3-phosphate to Chorismate;
ix. a Anthranilate synthase converting Chorismate to Anthranilate;
x. a Ribose-phosphate pyrophosphokinase converting Ribose-5-phosphate to Phospho-alpha-D-ribosyl-1-pyrophosphate;
xi. a Anthranilate phosphoribosyl transferase converting Anthranilate and Phospho-alpha-D-ribosyl-1-pyrophosphate to N-(5-phosphoribosyl)-anthranilate;
xii. a N-(5′-phosphoribosyl)-anthranilate isomerase converting N-(5-phosphoribosyl)-anthranilate to 1-(o-carboxyphenylamino)-1′-deoxyribulose 5′-phosphate;
xiii. an Indole-3-glycerol phosphate synthase converting 1-(o-carboxyphenylamino)-1′-deoxyribulose 5′-phosphate to (1S,2R)-1-C-(indol-3-yl)-glycerol 3-phosphate;
xiv. a Tryptophan synthase converting (1S,2R)-1-C-(indol-3-yl) glycerol 3-phosphate and Serine to L-Tryptophan;
and/or
xv. a Tryptophan decarboxylase converting L-Tryptophan to Tryptamine;
and
b) a heterologous Tryptamine 5-hydroxylase converting tryptamine to serotonin;
and
c) a heterologous Cytochrome p450 reductase assisting the conversion of tryptamine to serotonin by a Tryptamine 5-hydroxylase.

18 more elements

A genetically modified microbial host cell producing a psilocybin indole acceptor expressing

a) one or more enzymes selected from
i. one or more enzymes converting glucose to fructose-6-phosphate;
ii. a fructose-6-phosphate phosphoketolase converting fructose-6-phosphate to Erythrose-4-phosphate and acetyl phosphate;
iii. a Phosphotransacetylase converting Acetyl phosphate to Acetyl-CoA;
iv. one or more enzymes converting Fructose-6-phosphate to Phosphoenolpyruvate;
v. a 3-deoxy-D-arabino-heptulosonate 7-phosphate synthase (DAHP synthase) converting Phosphoenolpyruvate and Erythrose-4-phosphate to 3-deoxy-D-arabino-heptulosonate-7-phosphate (DAHP);
vi. one or more enzymes converting 3-deoxy-D-arabino-heptulosonate-7-phosphate to 5-enolpyruvoyl-shikimate 3-phosphate;
vii. a Shikimate kinase converting Shikimate to Shikimate-3-phosphate;
viii. a Chorismate synthase converting 5-enolpyruvoyl-shikimate 3-phosphate to Chorismate;
ix. a Anthranilate synthase converting Chorismate to Anthranilate;
x. a Ribose-phosphate pyrophosphokinase converting Ribose-5-phosphate to Phospho-alpha-D-ribosyl-1-pyrophosphate;
xi. a Anthranilate phosphoribosyl transferase converting Anthranilate and Phospho-alpha-D-ribosyl-1-pyrophosphate to N-(5-phosphoribosyl)-anthranilate;
xii. a N-(5′-phosphoribosyl)-anthranilate isomerase converting N-(5-phosphoribosyl)-anthranilate to 1-(o-carboxyphenylamino)-1′-deoxyribulose 5′-phosphate;
xiii. an Indole-3-glycerol phosphate synthase converting 1-(o-carboxyphenylamino)-1′-deoxyribulose 5′-phosphate to (1S,2R)-1-C-(indol-3-yl)-glycerol 3-phosphate;
xiv. a Tryptophan synthase converting (1S,2R)-1-C-(indol-3-yl) glycerol 3-phosphate and Serine to L-Tryptophan;
and/or
xv. a Tryptophan decarboxylase converting L-Tryptophan to Tryptamine;
and
b) a Tryptamine 4-hydroxylase converting tryptamine to 4-hydroxytryptamine;
c) a Cytochrome p450 reductase assisting tryptamine 4-hydroxylase in converting tryptamine to 4-hydroxytryptamine;
d) a Cytochrome b5 assisting tryptamine 4-hydroxylase in converting tryptamine to 4-hydroxytryptamine;
e) 4-hydroxytryptamine kinase converting 4-hydroxytryptamine to Norbaeocystin;
and
f) Psilocybin synthase converting Norbaeocystin to Psilocybin.

21 more elements

Dependencies are inferred from the claim text.

Methods for producing tryptamine derivatives

Life of this patent

Methods for producing tryptamine derivatives

Life of this patent

Abstract

Claims159