Application | Comment | Organism |
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medicine | a Saccharomyces cerevisiae strain is engineered to express seven heterologous enzymes (Papaper somniferum norcoclaurine 6-O-methyltransferase (Ps6OMT), Papaver somniferum 3'-hydroxy-N-methylcoclaurine 4'-O-methyltransferase 2 (Ps4'OMT), Papapver somniferum coclaurine N-methyltransferase (PsCNMT), Papaver somniferum berberine bridge enzyme (PsBBE), Thalictrum flavum scoulerine 9-O-methyltransferase (TfS9OMT), Thalictrum flavum canadine synthase (TfCAS), and Arabidopsis thaliana cytochrome P450 reductase 1 (CPR)), resulting in protoberberine alkaloid production from a simple benzylisoquinoline alkaloid precursor. A number of strategies are implemented to improve flux through the pathway, including enzyme variant screening, genetic copy number variation, and culture optimization. This leads to an over 70-fold increase in canadine titer up to 1.8 mg/l. Increased canadine titers enable extension of the pathway to produce berberine, a major constituent of several traditional medicines in a microbial host. This strain is viable at pilot scale | Thalictrum flavum subsp. glaucum |
Cloned (Comment) | Organism |
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canadine-producing Saccharomyces cerevisiae strain harbors expression cassettes for seven heterologous enzymes: Papaper somniferum norcoclaurine 6-O-methyltransferase (Ps6OMT), Papaver somniferum 3'-hydroxy-N-methylcoclaurine 4'-O-methyltransferase 2 (Ps4'OMT), Papapver somniferum coclaurine N-methyltransferase (PsCNMT), Papaver somniferum berberine bridge enzyme (PsBBE), Thalictrum flavum scoulerine 9-O-methyltransferase (TfS9OMT), Thalictrum flavum canadine synthase (TfCAS), and Arabidopsis thaliana cytochrome P450 reductase 1 (CPR). The expression cassettes for the methyltransferases Ps6OMT, PsCNMT, and Ps4'OMT and the cytochrome P450 reductase CPR were chromosomally integrated, TfS9OMT and TfCAS are expressed from a high-copy plasmid, and PsBBE is expressed from a second high-copy plasmid | Thalictrum flavum subsp. glaucum |
Localization | Comment | Organism | GeneOntology No. | Textmining |
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membrane | bound to | Thalictrum flavum subsp. glaucum | 16020 | - |
Organism | UniProt | Comment | Textmining |
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Thalictrum flavum subsp. glaucum | Q5C9L1 | - |
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