Compositions and methods for making alkaloid morphinans

1. A method of making a second morphinan having a C 7 -C 8 saturated carbon bond and a C 8 -C 14 mono-unsaturated carbon bond comprising:

(a) providing a first morphinan having a C 7 -C 8 mono-unsaturated carbon bond and a C 8 -C 14 saturated carbon bond; and

(b) contacting the first morphinan with a codeine isomerase or codeinone reductase capable of converting the first morphinan into the second morphinan;

wherein

the first morphinan has the chemical formula (V)

and wherein the second morphinan has the chemical formula (VI)

and wherein in the first and second morphinan R 1 is a methoxy group, R 2 is a hydroxyl group and R 2 ′ a hydrogen atom;

or

the first morphinan has the chemical formula (V)

and wherein the second morphinan has the chemical formula (VI)

and wherein in the first and second morphinan R 1 is a hydroxyl group, R 2 is a hydroxyl group and R 2 ′ is a hydrogen atom;

or

the first morphinan has the chemical formula (VII)

and wherein the second morphinan has the chemical formula (VIII)

and wherein in the first and second morphinan R 1 is a methoxy group, R 2 is a hydroxyl group and R 2 ′ is a hydrogen atom;

or

the first morphinan has the chemical formula (VII)

and wherein the second morphinan has the chemical formula (VIII)

and wherein in the first and second morphinan R 1 is a hydroxyl group, R 2 is a hydroxyl group and R 2 ′ is a hydrogen atom;

or

the first morphinan has the chemical formula (IX)

and wherein the second morphinan has the chemical formula (X)

and wherein in the first and second morphinan R 1 is a methoxy group, R 2 is a hydroxyl group and R 2 ′ is a hydrogen atom;

or

the first morphinan has the chemical formula (IX)

and wherein the second morphinan has the chemical formula (X)

and wherein in the first and second morphinan R 1 is a hydroxyl group, R 2 is a hydroxyl group and R 2 ′ is a hydrogen atom.

2. The method according to claim 1 further comprising a step (c) recovering the second morphinan.

3. A method for preparing a morphinan having chemical formula (II)

wherein, R 1 represents a hydroxyl group or a methoxy group; wherein R 2 represents a hydroxyl group and R 2 ′ represents a hydrogen atom; and wherein R 3 represents a hydrogen atom, or a methyl group, wherein when R 3 represents a methyl group, the nitrogen atom bonded to R 3 is optionally in the form of an N-oxide; and wherein the method comprises:

(a) providing a chimeric nucleic acid sequence comprising as operably linked components:

(i) a nucleic acid sequence encoding a codeine isomerase polypeptide or codeinone reductase polypeptide;

(ii) one or more nucleic acid sequences capable of controlling expression in a host cell;

(b) introducing the chimeric nucleic acid sequence into a host cell that endogenously produces or is exogenously supplied with a morphinan substrate;

(c) growing the host cell to produce codeine isomerase or codeinone reductase and to produce the morphinan having chemical formula (II); and

(d) recovering the morphinan having chemical formula (II) from the cell.

4. The method according to claim 3 , wherein the nucleic acid sequence encoding the codeine isomerase comprises SEQ. ID. NO: 1 or a functional variant thereof, and wherein the nucleic sequence encoding the codeinone reductase comprises SEQ. ID NO: 5 or a functional variant thereof.

5. The method according to claim 3 wherein the cell is a bacterial cell, a yeast cell or a plant cell.

6. The method according to claim 3 wherein the morphinan substrate has the chemical formula (I)

wherein in chemical formula (I), R 1 represents a hydroxyl group or a methoxy group; wherein R 2 represents a hydroxyl group and R 2 ′ represents a hydrogen atom; and wherein R 3 represents a hydrogen atom, or a methyl group, wherein when R 3 represents a methyl group, the nitrogen atom bonded to R 3 is optionally in the form of an N-oxide.