Stratégies to improve the production of secondary metabolites with plant cell cultures : a literature review
The production of secondary metabolites using plant cells has been the subject of much research in recent years. The expectations were high since the market introduction of the first commercial product made with this technique, shikonin made with cell cultures of Lithospermum erythrorhizon in Japan. In spite of the huge amount of effort that has been put into research into this topic, not many products have reached the commercial stage since then. It is generally acknowledged that the main problem in this field is the lack of basic knowledge of the biosynthetic routes, and the mechanisms behind the production of secondary metabolites. There are, however, some techniques that have beneficial effects on the production and excretion in many cases, and they will be reviewed in this paper. The subjects treated will be the immobilization of plant cells, the use of two-phase systems to enhance the excretion of secondary metabolites, the use of selected reactors for the growth of the cells and the production of secondary metabolites, models that describe the phenomena during growth and production, and the commercial processes that exist at this moment, including some economic considerations. More techniques exist to enhance growth, production and excretion, but they do not fit into the scope of this review. Examples are elicitation, cell line selection or genetic manipulation of the plant cells. Although the discussed strategies have proven to work in a number of cases, there is still no general approach that guarantees a long-term, high producing