Biosynthesis in plants and metabolic engineering for their biotechnological production

Abstract

In the present chapter, we review some aspects of sesquiterpene lactones biosynthesis regulation in different medicinal and aromatics plant used in the pharmaceutical industry. That includes, the mevalonate pathway and the 2-C-methyl-D-erythritol 4-phosphate pathway involved in isoprenoids precursors production (isopentenyl diphosphate and dimethylallyl diphosphate) as well as the late pathways that lead with STL biosynthesis. The chapter also describe the transcription factors, which regulate sesquiterpene lactones biosynthesis and have been recently isolated and characterized by different research groups.We also review the different biotechnological approaches that have been developed for their production. In vitro plant cell cultures, comprising micropropagation, plant cell suspension, shoot and root cultures, offer controlled system and shorter production cycles and emerged as the first strategy as a production platform for many plant secondary metabolites. The characterization and isolation of genes involved in the regulation of sesquiterpene lactones biosynthetic pathways allowed the design of metabolic engineering strategies to increase the production of these metabolites. We discuss the different strategies performed to increase sesquiterpene lactones production by means of genetic engineering. An especial focus in the metabolic engineering of the artemisinin biosynthetic pathway in Artemisia annua is discussed. This metabolic pathway has become as a model system not only for the biotechnological production of sesquiterpene lactones but also for the improvement of other plant secondary metabolic pathways. Finally, we discuss the successful expression of the complete artemisinin biosynthetic pathway in Escherichia coli and Saccharomyces cerevisiae, which lead to the efficient accumulation of artemisinic acid in these microorganisms.