Plant cells: secondary metabolite heterogeneity and its manipulation.

This chapter proposes the concept of rational manipulation of secondary metabolite heterogeneity in plant cell cultures. The heterogeneity of plant secondary metabolites is a very interesting and important issue because these structure-similar natural products have different biological activities. Both taxoids and ginsenosides are two kinds of preeminent examples in the enormous reservoir of pharmacologically valuable heterogeneous molecules in the plant kingdom. They are derived from the five-carbon precursor isopentenyl diphosphate, produced via the mevalonate or the non-mevalonate pathway. The diterpenoid backbone of taxoids is synthesized by taxadiene synthase and the triterpenoid backbone of ginsenosides is synthesized by dammarenediol synthase or beta-amyrin synthase. After various chemical decorations (oxidation, substitution, acylation, glycosylation, benzoylation, and so on) mediated by P450-dependent monooxygenases, glycosyltransferases, acyltransferases, benzoyltransferases, and other enzymes, the terpenoid backbones are converted into heterogeneous taxoids and ginsenosides with different bioactivities. Although detailed information about accumulation and regulation of individual taxoids or ginsenosides in plant cells is still lacking, remarkable progress has recently been made in the structure and bioactivity identification, biosynthetic pathway, manipulation of their heterogeneity by various methodologies including environmental factors, biotransformation, and metabolic engineering in cell/tissue cultures or in plants. Perspectives on a more rational and efficient process to manipulate production of desired plant secondary metabolites by means of metabolic engineering and "omics"-based approaches (e.g., functional genomics) are also discussed.