Scheme 1
From: Optimization of yeast-based production of medicinal protoberberine alkaloids
Heterologous berberine biosynthetic pathway from norlaudanosoline. Shown is the conversion of rac-norlaudanosoline to (S)-reticuline via the SAM-dependent methyltransferases norcoclaurine 6-O-methyltransferase (6OMT), 3′-hydroxy-N-methylcoclaurine 4′-O-methyltransferase (4′OMT), and coclaurine-N-methyltransferase (CNMT), and to the protoberberine alkaloids (S)-scoulerine via berberine bridge enzyme (BBE), (S)-tetrahydrocolumbamine via scoulerine 9-O-methyltransferase (S9OMT), (S)-canadine via canadine synthase (CAS) and its reductase partner cytochrome P450 reductase (CPR), and berberine via (S)-tetrahydroprotoberberine oxidase (STOX) or spontaneous oxidation