Progress in the production of medicinally important secondary metabolites in recombinant microorganisms or plants-Progress in alkaloid biosynthesis
Résumé
Plants produce a high diversity of natural products or secondary metabolites which are important for the communication of plants with other organisms. A prominent function is the protection against herbivores and/or microbial pathogens. Some natural products are also involved in defence against abiotic stress, e.g. UV-B exposure. Many of the secondary metabolites have interesting biological properties and quite a number are of medicinal importance. Because the production of the valuable natural products, such as the anticancer drugs paclitaxel, vinblastine or camptothecin in plants is a costly process, biotechnological alternatives to produce these alkaloids more economically become more and more important. This review provides an overview of the state of art to produce alkaloids in recombinant microorganisms, such as bacteria or yeast. Some progress has been made in the metabolic engineering usually employing a single recombinant alkaloid gene. More importantly, for benzylisoquinoline, monoterpene indole and diterpene alkaloids (taxanes) as well as some terpenoids and phenolics the proof of concept for the production of complex alkaloids in recombinant E. coli and yeast has already been achieved. In a long-term perspective, it will probably be possible generate gene cassettes for complete pathways which could then be used for the production of valuable natural products in bioreactors or for metabolic engineering of crop plants to improve their resistance against herbivores and/or microbial pathogens.
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