Unnatural Sources of Plant Secondary Metabolites

Plant tissue cultures are generally carried out in a liquid medium, using cell suspensions to provide uniform conditions and support a faster growth in an 

The first plant product commercially produced by plant cell culture was the prenylated anthraquinone shikonin 16, from the boraginaceous plant Lithospermum erythrorhizon Sieb. et Zucc. (Mitsui Petrochemical Industry Company) in 1983.25 Shikonin is used as a dye in cosmetics (lipsticks, soaps and lotions) and its production yield from cell cultures was over ten-fold its isolation yield from the intact plant.25 In practice, eight runs of two weeks each in a 200 L bioreactor could afford the amount of shikonin produced in four years by a 1 ha field of L. erythrorhizon 25 Shikonin has an interesting and pleiotropic biological profile, which includes insulin mimicry and interference with protein-protein interactions, but it has not yet found medicinal application.26 

To increase production and facilitate isolation, plant cells have been immobilised on various matrices such as polyurethane foam and calcium alginate gel beads,24 while elicitation (i.e. the induction of a defence response) is generally critical for the production of secondary metabolites. The rationale for the use of elicitors is that plants produce secondary metabolites as part of a defence response to stress, either biotic (pathogen infection) or abiotic (ultraviolet, toxic heavy metals and rare earth ions). Jasmonic acid plays a crucial role in plant stress responses and, along with fungal polysaccharides and heavy metals, is the most widely employed elicitor in plant tissue cultures.30 

Natural products can also be obtained from a direct biotechnological route where all the genes involved in the biosynthesis are expressed in a fermentable 

Finally, fermentation of endophytic fungi from higher plants has also been considered for the production of plant natural products. Fungal fermentation is much simpler than plant tissue culture but, at least for paclitaxel, production by fermentation of various Taxus endophytic fungi was lower compared with that of plant cells.35 

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