TY - JOUR
T1 - Metabolic engineering with a morphine biosynthetic P450 in opium poppy surpasses breeding
AU - Frick, Susanne
AU - Kramell, Robert
AU - Kutchan, Toni M.
N1 - Funding Information:
We thank Philip Larkin and his co-workers from CSIRO Plant Industry for the opportunity to learn their transformation protocol of opium poppy. We are also grateful to Dr. Tony Fist from Tasmanian Alkaloids Pty Ltd for the donations of seeds from the opium poppy inbreed line CO48-6-14-64. We thank Kathleen Bräuer and Elke Hillert for cell culture work, Heike Riegler for preparation of Southern blots and Christine Kaufmann for assistance with graphs. This project was funded by Deutsche Forschungsgemeinschaft (DFG), Bonn, and Fonds der chemischen Industrie, Frankfurt, Germany.
PY - 2007/3
Y1 - 2007/3
N2 - Morphine biosynthesis was genetically engineered in an industrial elite line of the opium poppy (Papaver somniferum L.), to modify the production of alkaloids in plants. The cytochrome P-450-dependent monooxygenase (S)-N-methylcoclaurine 3′-hydroxylase (CYP80B3) lies on the pathway to the benzylisoquinoline alkaloid branch point intermediate (S)-reticuline. Overexpression of cyp80b3 cDNA resulted in an up to 450% increase in the amount of total alkaloid in latex. This increase occurred either without changing the ratio of the individual alkaloids, or together with an overall increase in the ratio of morphine. Correspondingly, antisense-cyp80b3 cDNA expressed in opium poppy caused a reduction of total alkaloid in latex up to 84%, suggesting that the observed phenotypes were dependent on the presence of the transgene. This study found compelling evidence, that cyp80b3 is a key regulation step in morphine biosynthesis and provides practical means to genetically engineer valuable secondary metabolites in this important medicinal plant.
AB - Morphine biosynthesis was genetically engineered in an industrial elite line of the opium poppy (Papaver somniferum L.), to modify the production of alkaloids in plants. The cytochrome P-450-dependent monooxygenase (S)-N-methylcoclaurine 3′-hydroxylase (CYP80B3) lies on the pathway to the benzylisoquinoline alkaloid branch point intermediate (S)-reticuline. Overexpression of cyp80b3 cDNA resulted in an up to 450% increase in the amount of total alkaloid in latex. This increase occurred either without changing the ratio of the individual alkaloids, or together with an overall increase in the ratio of morphine. Correspondingly, antisense-cyp80b3 cDNA expressed in opium poppy caused a reduction of total alkaloid in latex up to 84%, suggesting that the observed phenotypes were dependent on the presence of the transgene. This study found compelling evidence, that cyp80b3 is a key regulation step in morphine biosynthesis and provides practical means to genetically engineer valuable secondary metabolites in this important medicinal plant.
KW - Metabolic engineering
KW - Morphine biosynthesis
KW - Opium poppy
KW - P450 enzyme
KW - Somatic embryogenesis
KW - Transformation
UR - http://www.scopus.com/inward/record.url?scp=33847279410&partnerID=8YFLogxK
U2 - 10.1016/j.ymben.2006.10.004
DO - 10.1016/j.ymben.2006.10.004
M3 - Article
C2 - 17189709
AN - SCOPUS:33847279410
SN - 1096-7176
VL - 9
SP - 169
EP - 176
JO - Metabolic Engineering
JF - Metabolic Engineering
IS - 2
ER -