Engineering Formation of Medicinal Compounds in Cell Cultures

Higher plants are rich sources of medicinal compounds. Many medicinal plants, however, are still harvested in the wild due to technical difficulties of cultivation, as well as for economic reasons. The increased demand and drastic reduction in plant availability increase the pressure to produce medicinal compounds via alternative ways, especially using cell/tissue cultures and transgenic plants. Furthermore, the demands for quality materials have also increased. Before 1970, the reported yields from cell cultures were generally lower than those in plants. However, several cell cultures can have considerable productivity, and in some cases their production exceeds that present in intact plants. The current advancements in understanding and manipulating the molecular and cellular biology of secondary metabolism provide a basis for optimism regarding the commercial production of secondary products in cell/organ cultures and/or transgenic plants. We summarize recent progress in alkaloid research as a principal model and discuss the factors that control productivity and quality, focusing on organ differentiation, genetic instability, rate-limiting enzyme steps in metabolism, transcriptional regulators, transport, and storage.

Key Words: Secondary metabolite, Plant cell culture, Metabolic engineering, RNA interference (RNAi), Expressed sequence tag (EST), Organ differentiation, Compartmentalization, Cell-specific gene expression, Biosynthetic pathway, Isoquinoline alkaloid, Terpenoid indole alkaloid, Tropane alkaloid.

Abbreviations: TYDC, Tyrosine/dopa decarboxylase; NCS, Norcoclaurine synthase; SAM, S-adenosyl methionine; 6OMT, Norcoclaurine 6-O-methyltransferase; 4'OMT, 3' hydroxy N-methylcoclaurine 4'-O-methyltransferase; BBE, Berberine bridge enzyme; CDS, Canadine synthase; SOMT, Scoulerine 9-O-methyltransferase; SAT, Acetylcoenzyme A:salutaridinol-7-O-acetyltransferase; COR, Codeinone reductase; STR, Strictosidine synthase; TDC, Tryptophan decarboxylase; G10H, Geraniol 10-hydroxylase; CYP72A1, Secologanin synthase; SGD, Strictosidine glucosidase; T16H, Tabersonine 16-hydroxylase; PCR, Polymerase chain reaction; CPR, Cytochrome P450 reductase; D4H, Desacetoxyvindoline 4-hydroxylase; DAT, Acetylcoenzyme A: deacetylvindoline 4-O-acetyltransferase; ODC, Ornithine decarboxylase; ADC, Arginine decarboxylase; PMT, Putrescine N-methyltransferase; GUS, β-glucuronidase; TR-I/II, Tropinone reductase I/II; H6H, Hyoscyamine 6β-hydroxylase; MeJA, Methyl jasmonate; SA, Salicylic acid; EST, expressed sequence tag; AFLP, amplified fragment length polymorphism.