Oxygen requirements for lipid biosynthesis in yeast

Abstract

The yeast Saccharomyces cerevisiae has been used by humans for many centuries in microbial fermentation processes for the production of, for example, bread and alcoholic beverages. This long history of use and, in addition, its fast growth, its ability to rapidly convert sugars into ethanol and the ease with which it can be genetically modified, have contributed to this yeast becoming a very popular model organism. S. cerevisiae is currently used in large-scale industrial processes for the production of biofuels and a broad range of other chemicals. The ability of S. cerevisiae to grow in the absence of oxygen is quite unique among yeasts, and not only important for the production of beer and wine, but also for industrial production of bulk chemicals. The high product yields that are required in these types of processes can in theory only be achieved when sugars are completely converted into product, instead of being partially or completely oxidized to CO2 via aerobic respiration. Fast anaerobic growth of S. cerevisiae does require that standard synthetic media, that are used to grow this yeast in the laboratory, are supplemented with a number of additional components. These additional nutritional requirements originate from the fact that oxygen is required for biosynthesis of some important components of the yeast cell. While most yeast species are actually able to ferment, they usually cannot grow in the complete absence of oxygen at all, not even when such cell components or their precursors are added to anaerobic growth media. As a consequence, some yeast species that have industrially relevant traits that are absent or less pronounced in S. cerevisiae, such as resistance to higher temperatures, cannot at the moment be used in anaerobic industrial processes. This PhD thesis describes research on oxygen requirements related to membrane synthesis in yeast, using S. cerevisiae as the main model organism, with the goal to understand these requirements and eliminate them by genetic modification. Inspiration is obtained from evolutionary adaptations of eukaryotic microorganisms that naturally occur in anaerobic or oxygen-poor environments. Metabolic engineering strategies developed in this way may then possibly be applied to other industrially relevant yeast species and thus aid the elucidation of additional, as yet unknown oxygen requirements, or even enable anaerobic growth of those yeasts as well.