Methods of producing morphinan alkaloids and derivatives

An engineered non-plant cell, comprising:

• i) an engineered epimerase, wherein the engineered epimerase converts an (S)-1-benzylisoquinoline precursor to an (R)-1-benzylisoquinoline product;
• ii) a thebaine synthase;
• and
• iii) at least one modification selected from the group consisting of:
• a) a substrate inhibition alleviating mutation, b) a product inhibition alleviating mutation, c) a cofactor recovery promoting mechanism, d) a feedback inhibition alleviating mutation, e) transcriptional modulation modification, and f) an inactivating mutation;
• wherein, within the engineered non-plant cell, the engineered non-plant cell converts a precursor of a promorphinan molecule to an alkaloid product selected from the group consisting of:
• i) a morphinan alkaloid, ii) a nal-opioid alkaloid, and iii) a nor-opioid alkaloid.