ABSTRACT
Fatty acyl CoAs represent bioactive compounds that are involved in intracellular transport, cellular signalling, endocytosis and transcriptional control, as well as serving as substrates for -oxidation and biosynthesis of phospholipids, sphingolipids and sterols. Metabolic engineering of Saccharomyces cerevisiae has been successful for the production of metabolites and therapeutic proteins but has not yet been used for the production of lipid-derived compounds. Extensive incorporation of triglyceride fatty acids into yeast can be achieved by growing the cells in the presence of triacylglycerols and exogenously supplied lipase, thus opening up an avenue for the bioconversion of low-cost oils into value-added lipid products (Dyer et al., 2002). Recently, a remarkable feat of metabolic manipulation in yeast (Szczebara et al., 2003) has been achieved: researchers took advantage of the fact that yeast cannot synthesise complex steroids and introduced into the yeast cell an altered sterol pathway whose end product was hydrocortisone, an anti-inflammatory steroid hormone for treatment of arthritis or progesterone for the production of vitamin D2. This ‘tour de force’ of metabolic engineering was successful because all the genes of the sterol biosynthetic pathway are known in yeast and genetic manipulation allowed removal of undesirable gene products and exploited the flexibility of localisation and trafficking of sterol intermediates. In this chapter, the central role and impact of lipid metabolism on yeast physiology will be presented.
