Enhancement of rosmarinic acid content by biotechnological approaches and metabolic engineering

Various secondary metabolites having medicinal values are isolated from different medicinal plants. Rosmarinic acid is a dimer of caffeic acid, and a vital antioxidant reported with numerous biological properties, such as anticancer, antimicrobial, analgesic, etc. Initially, rosmarinic acid was isolated from rosemary (Rosmarinus officinalis) belonging to the family, Lamiaceae. Subsequently, the existence of rosmarinic acid was identified in different medicinal plants, such as basil, salvia, lavender, etc., belonging to the families, Lamiaceae and Boraginaceae. The low content of rosmarinic acid in field-grown plant parts and seasonal variation are the major limitations of its continuous supply for medicinal purposes. Alternatively, plant tissue culture is a superior and attractive strategy to enhance the rosmarinic acid content. The cell culture technique facilitates sustainable production of rosmarinic acid in a controlled environment, and it is well established. To enhance the rosmarinic acid content in herbs different tissue culture approaches, such as callus induction, hairy root culture, Agrobacterium infection induced callus, precursors (phenylalanie and tyrosine) addition in callus suspension culture, and elicitation by supplementing yeast extract and methyl jasmonate in callus suspension have been followed by several researchers. Further metabolic engineering is the promising approach where expression of rate limiting enzymes of rosmarinic acid synthesis pathway is over expressed by molecular cloning. Phenylalanine ammonia-lyase (PAL) and tyrosine aminotransferase (TAT) are well-known enzymes involved in rosmarinic acid biosynthesis. PAL and TAT are well characterized at molecular level, and their overexpression facilitated increases in biosynthesis of rosmarinic acid (RA) in different plants. Thus, the purpose of this chapter is to explore the biological activity of rosmarinic acid and its production enhancement through various biotechnological approaches including plant cell culture, elicitation, hairy root culture, and metabolic engineering.