Secondary metabolites from numerous plant sources have been developed as anti-
cancer reagents and compounds such as resveratrol, podophyllotoxin and zerumbone are
of particular importance in this regard. Since their de novo chemical synthesis is both arduous
and commercially expensive, there has been an impetus to develop viable, biotechnological
methods of production. Accordingly, this review focuses on the recent developments
in the field, highlighting the use of micropropagation, cell suspension cultures, callus
cultures, hairy root cultures, recombinant microbes and genetically modified higher plants.
Optimization of media and culture conditions, precursor feeding, immobilization and the
use of chemical or physical elicitation in various protocols has led to an increase in resveratrol
and podophyllotoxin production. Heterologous gene transformation of higher plants
with stilbene synthase derived from Arachis hypogaea or Vitis vinifera lead to resveratrol
production with the concomitant increase in resistance to plant pathogens. Interestingly,
genetic transformation of Podophyllum hexandrum and Linum flavum with Agrobacterium
rhizogenes resulted in Ri-T-DNA gene(s)-mediated enhancement of podophyllotoxin production.
Zerumbone yields from tissue cultured plantlets or from suspension cultures are
generally low and these methods require further optimization. In microbes lacking the native
resveratrol or zerumbone biosynthesis pathway, metabolic engineering required not only
the introduction of several genes of the pathway, but also precursor feeding and optimization
of gene expression to increase their production. Data pertaining to safety and toxicity
testing are needed prior to use of these sources of anti-cancer compounds in therapy.
Keywords: Resveratrol, podophyllotoxin, zerumbone, anti-cancer agents, metabolic engineering, cell suspension
culture, elicitation, hairy root culture.
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