Metabolic Engineering For Improvement Of Productivity

With the advent of molecular biology and the possibility of genetically transforming plant cells and obtaining genetically modified (GM) or transgenic plants therefrom, there has been increased interest in improving the productivity and/or quality not only of arable crops but also—to a lesser extent— of medicinal plant species. In addition, molecular biology provides the possibility to transfer single or multiple genes encoding biosynthetic enzymes into microorganisms with the purpose of secondary metabolite production.

The general strategies for the biotechnological exploitation of alkaloid biosynthetic genes have been summarized by Kutchan (11), but they also apply for other secondary metabolites (Fig. 3). Plant secondary metabolite genes can be functionally expressed in microorganisms to produce either single biotransformation steps or short biosynthetic pathways. This approach requires that sufficient quantities of the secondary metabolite precursors needed for biotransformation are available at low cost. Promising results have been achieved in the laboratory of Verpoorte (2), who succeeded in the functional expression of the biosynthetic genes for strictosidine synthase and strictosidine glucosidase in transgenic yeast. After addition of tryptamin to the transgenic yeast cultures growing in a medium containing a secologanin-rich extract of snowberries, strictosidine and cathenamine, both precursors of the potent anticancer alkaloids vinblastine and vincristine, were obtained in high yield (12). However, this approach is difficult or impossible if biosynthetic enzymes are involved that require plant-specific glycosylation for their activity. In this case, metabolic engineering will be restricted to plants or plant cells. As shown in Fig. 3, overexpression of single biosynthetic genes in plants or plant cells may yield enhanced amounts of the desired secondary metabolites within a pathway or even novel secondary metabolites

Microorganisms Plant pathway: p

Single gene expression for biomimetic syntheses

Plants

Heterologous Overexpression Antisense or Gene ofbiosynthetic Cosuppression

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