Isoprenoids are a large class of, mainly plant-derived natural compounds. Also known as terpenoids. they comprise more than 55,000 compounds and constitute one of the largest classes of metabolites in nature. Their importance stems from their diverse uses in fields like nutrition and medicine, with some of these compounds, such as taxol and artemisinin, currently being used as pharmaceuticals for the treatment of cancer and malaria, respectively, with numerous other applications under investigation. Despite strong interest in these compounds, current methods of production rely on extraction from plant sources, which are inefficient, unreliable and costly. As a result, effective drugs cannot be deployed at scale especially in developing countries due to high cost. In recent years microbial metabolic engineering has made great advances in facilitating the biosynthesis of isoprenoids. In this talk, I will outline general principles of metabolic engineering for isoprenoid production in <i>Escherichia coli</i> and the oleaginous yeast <i>Yarrowia lipolytica</i> that yielded record levels of taxadiene accumulation. A new pathway bypassing central carbon metabolism will be described along with methods to overcome the hydrophobic nature of these compounds which prevents their intracellular accumulation to very high levels. Due, in part, to these advances, a pipeline of isopreboid products has been constructed for their cost effective production by microbial fermentation.

B&B Gaden Award: Engineering microbes for the production of isoprenoid compounds

2019 Spring National Meeting

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