The most common problems for the commercial application of metabolite
production in cell culture systems are low productivity and the high cost associated
with the maintenance of cell cultures, compared to harvesting in the field;
for example, morphine is not produced in cultured Papaver cells and only low
levels of vinblastine are produced in cultured Catharanthus cells. However, molecular
engineering is a powerful tool and may be able to overcome these problems.
First, other aspects of cell culture will need to be clarified for production.
For example, while it is clear that selected cultured Coptis cells are superior
to naturally grown Coptis rhizomes with regard to berberine production
and uniform metabolite composition, these cultured cells are not accepted as
being equivalent to natural rhizome. Since it has often been reported that In vitro-cultured cells/tissues have different metabolite profiles than intact tissues
(Fu, 1998; Yamazaki et al., 2003), the safety of these materials for direct use as
natural medicines has been questioned. Thus, cultured cells require additional
certification to be considered equivalent to Coptis rhizome. On the other hand,
the costs of tedious downstream processing to purify berberine from cultured Coptis cells cannot compete with that obtained by wild harvest from other sources,
if metabolic engineering is not applicable. The size of the anticipated market is
another important factor for commercialization.
So far, three metabolites produced in cultured cells/roots have been reported
to be successfully commercialized (Table 11.1). One is cultured ginseng, the
extract of which has been approved as a food additive with a market of $3 million
in 1995 (Fu, 1998). The other two products are used in cosmetics: polysaccharides
produced by cultured Polyanthes tuberosa cells (Honda et al., 1996) and Saiko
extracts from cultured Saiko (Bupleurum falcatum L.) roots (Kusakari et al., 2000).
In the latter cases, researchers found that polysaccharides and saikosaponins had
novel activities regarding skin protection and developed their use as cosmetics. These successes clearly indicate that the discovery of novel product activities is
essential for commercial development, except for a few chemicals such as paclitaxel,
which have a high price and high demand. Functional evaluation of the
metabolic profile in plant cells is crucial for the future engineering of medicinal