Processes for the production of tryptamines
AssigneeCompass Pathfinder Limited
InventorRyan Protzko
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Abstract
Disclosed herein are prokaryotic and eukaryotic microbes, including E. coli and S. cerevisiae, genetically altered to biosynthesize tryptamine and tryptamine derivatives. The microbes of the disclosure may be engineered to contain plasmids and stable gene integrations containing sufficient genetic information for conversion of an anthranilate or an indole to a tryptamine. The fermentative production of substituted tryptamines in a whole-cell biocatalyst may be useful for cost effective production of these compounds for therapeutic use.
Claims11
A method of synthesizing a tryptamine derivative from a substituted tryptamine, the method comprising
- cultivating an engineered microbial cell comprising one or more nucleic acid sequences encoding one or more of:
- (i) a tryptamine 4-hydroxylase comprising an amino acid sequence having at least 80% sequence identity to any one of SEQ ID NOS:
- 32-35;
- (ii) a tryptamine 5-hydroxylase comprising an amino acid sequence having at least 80% sequence identity to SEQ ID NO:
- 47;
- (iii) a kinase comprising an amino acid sequence having at least 80% sequence identity to any one of SEQ ID NOS:
- 41-44;
- (iv) a P450 reductase comprising an amino acid sequence having at least 80% sequence identity to any one of SEQ ID NOS:
- 36-40;
- and
- (v) a transferase comprising an amino acid sequence having at least 80% sequence identity to any one of SEQ ID NOS:
- 21-31 or 46,
- in the presence of a substituted tryptamine to produce the tryptamine derivative, wherein:
- a) the substituted tryptamine comprises tryptamine, 5-hydroxytryptamine, or 5-phosphoryloxytryptamine, and the tryptamine derivative is:
- (5-phosphoryloxy-N-methyltryptamine);
- b) the substituted tryptamine comprises N,N-dipropyltryptamine or 4-hydroxy-N,N-dipropyltryptamine and the tryptamine derivative is:
- (4-phosphoryloxy-N,N-dipropyltryptamine);
- c) the substituted tryptamine comprises N,N-dipropyltryptamine or 5-hydroxy-N,N-dipropyltryptamine and the tryptamine derivative is:
- (5-phosphoryloxy-N,N-dipropyltryptamine);
- d) the substituted tryptamine comprises 7-hydroxytryptamine or 7-phosphoryloxytryptamine, and the tryptamine derivative is:
- (7-phosphoryloxy-N-methyltryptamine);
- e) the substituted tryptamine comprises ibogamine or 4-hydroxyibogamine, and the tryptamine derivative is:
- (4-phosphoryloxyibogamine) or
- (4-phosphoryloxyibogamine);
- f) the substituted tryptamine comprises ibogamine or 4-hydroxyibogamine, and the tryptamine derivative is:
- (4-methoxyibogamine);
- g) the substituted tryptamine comprises ibogamine and the tryptamine derivative is:
- (4-hydroxyibogamine) or
- (4-hydroxyibogamine);
- h) the substituted tryptamine comprises tryptamine, 4-hydroxytryptamine, 4-methoxytryptamine, 5-hydroxytryptamine, 5-methoxytryptamine, N,N-dimethyltryptamine, 4-hydroxy-N,N-dimethyltryptamine, 5-hydroxy-N,N-dimethyltryptamine, or 5-methoxy-N,N-dimethyltryptamine, and the tryptamine derivative is:
- (4,5-dimethoxy-N,N-dimethyltryptamine);
- or
- i) the substituted tryptamine comprises tryptamine, 4-hydroxytryptamine, or N-acetyltryptamine, and the tryptamine derivative is:
Dependencies are inferred from the claim text.