Methods of producing nor-opioid and nal-opioid benzylisoquinoline alkaloids
A method of demethylizing an opioid to a nor-opioid is provided. The method comprises contacting an opioid with at least one enzyme. Contacting the opioid with the at least one enzyme converts the opioid to a nor-opioid. A method of converting a nor-opioid to a nal-opioid is provided. The method comprises contacting a nor-opioid with at least one enzyme. Contacting the nor-opioid with the at least one enzyme converts the nor-opioid to a nal-opioid.
1. A method of demethylating an opioid to a nor-opioid, comprising:
contacting a first opioid with at least one enzyme within an engineered non-plant cell, wherein contacting the first opioid with the at least one enzyme converts the first opioid to a second opioid through loss of an O-linked methyl group; and
contacting the second opioid with at least one enzyme within the engineered non-plant cell, wherein contacting the opioid with the at least one enzyme converts the second opioid to a nor-opioid through loss of an N-linked methyl group.
2. The method of claim 1 , wherein the nor-opioid is produced by culturing the engineered non-plant cell comprising a coding sequence for encoding the first enzyme.
3. The method of claim 2 , further comprising:
recovering the nor-opioid from the cell culture.
4. The method of claim 2 , wherein the nor-opioid is produced within the engineered non-plant cell by a metabolic pathway starting with L-tyrosine.
5. The method of claim 2 , wherein the engineered non-plant cell is an engineered bacterial cell.
6. The method of claim 2 , wherein the engineered non-plant cell is an engineered yeast cell.
7. The method of claim 1 , wherein the loss of the O-linked methyl group occurs at the 3′ position.