1. Introduction

In spite of advances in synthetic organic chemistry, chemical synthesis of several compounds is not yet feasible due to their complex structures. The plants still contribute significantly to the bulk of the market products, such as secondary metabolites. The major limitations to the commercial use of potential metabolites is their very scarce supply from the field grown plants due to their seasonal growth, genetic, geographical and climatic variations, and insect and pathogen attack. The environmental fluxes cause alterations in type and quantity of metabolites produced. In this context, the cell culture technique is complimentary and may provide competitive metabolite production systems when compared to whole plant extraction. Since the plant cells are totipotent in nature, consequently, the cultured cells will also contain the genetic information for the production of therapeutic compounds with added potential of increasing yield by explants selection and manipulation of culture conditions. The cell cultures have several advantages over conventional isolation of metabolites from the intact plants, such as stable supply, freedom from disease and vagaries of climates, closer relationship between supply and demand, and growth of large amount of plant tissues in minimal space. Such an alternative method has considerable implication as it would reduce the pressure on natural population and, thus, may prevent the plant from becoming endangered. It may also help to steer clear of contaminated pharmaceutical raw material.

Also, studies on secondary metabolites require an in-depth understanding of biosynthetic pathways which is often difficult to conduct in whole plants because the biosynthetic activities may only be expressed in particular cell types within a specific plant organ or at a certain time of season. Cell cultures have a higher rate of metabolism than intact differentiated plants because the initiation of cell growth in culture leads to fast proliferation of cell mass and to a condensed biosynthetic cycle. As a result, secondary metabolite production can take place within a short cultivation time (about 2-4 weeks) with an added advantage of tunability. These cell cultures can be employed in scaled-up operation, for isolation of desirable compounds in bulk.

2.  History and evolution

Haberlandt attempted to cultivate isolated plant cells, but cell division was never observed in these cultures. In the 1930s the first in vitro cultures were established, and followed by the development of culture media and culture methods. Twenty-five years ago, the prospect of the use of plant cell cultures for metabolite production is not imaginable. The low yields of metabolite production in suspension cultures were the bottlenecks for commercialization. In such early efforts, plant cells in culture were treated in direct analogy to microbial systems, with little knowledge of plant cell physiology and biochemistry. In 1982, at least 30 compounds were known to accumulate in plant culture systems in concentrations equal to or higher than that of the plant. Concerning the production of natural metabolites, some in vitro systems exist that allow the large-scale production of economically important metabolites. A survey of the historical milestones in plant cell cultures is given by Schmauder and Doebel in 1990. Strategies to optimize growth and product formation began to develop separately during the period between 1975 and 1985. A combination of strategies for yield improvement resulted in the first commercial plant cell process.