Alkaloid biosynthesis in plants: Biochemistry, cell biology, molecular regulation, and metabolic engineering applications

Recent advances in the cell, developmental, and molecular biology of alkalo id biosynthesis have heightened our appreciation for the complexity and imp ortance of plant secondary pathways. Several biosynthetic genes involved in the formation of tropane, benzylisoquinoline, and terpenoid indole alkaloi ds have now been isolated. The early events of signal perception, the pathw ays of signal transduction, and the function of gene promoters have been st udied in relation to the regulation of alkaloid metabolism. Enzymes involve d in alkaloid biosynthesis are associated with diverse subcellular compartm ents including the cytosol, vacuole, tonoplast membrane, endoplasmic reticu lum, chloroplast stroma, thylakoid membranes, and perhaps unique "biosynthe tic" or transport vesicles. Localization studies have shown that sequential alkaloid biosynthetic enzymes can also occur in distinct cell types, sugge sting the intercellular transport of pathway intermediates. Isolated genes have also been used to genetically alter the accumulation of specific alkal oids and other plant secondary metabolites. Metabolic modifications include increased indole alkaloid levels, altered tropane alkaloid accumulation, e levated serotonin synthesis, reduced indole glucosinolate production, redir ected shikimate metabolism, and increased cell wall-bound tyramine formatio n. This review discusses the biochemistry, cell biology, molecular regulati on, and metabolic engineering of alkaloid biosynthesis in plants.