Metabolic engineering of plant alkaloid biosynthesis

Plant alkaloids, one of the largest groups of natural products, provide man y pharmacologically active compounds. Several genes in the biosynthetic pat hways for scopolamine, nicotine, and berberine have been cloned, making the metabolic engineering of these alkaloids possible. Expression of two branc hing-point enzymes was engineered: putrescine IV-methyltransferase (PMT) in transgenic plants of Atropa belladonna and Nicotiana sylvestris and (S)-sc oulerine 9-O-methyltransferase (SMT) in cultured cells of Coptis japonica a nd Eschscholzia californica. Overexpression of PMT increased the nicotine c ontent in RI. sylvestris, whereas suppression of endogenous PMT activity se verely decreased the nicotine content and induced abnormal morphologies. Ec topic expression of SMT caused the accumulation of benzylisoquinoline alkal oids in E. californica. The prospects and limitations of engineering plant alkaloid metabolism are discussed.