Glycerol as a substrate for Saccharomyces cerevisiae based bioprocesses - Knowledge gaps regarding the central carbon catabolism of this 'non-fermentable' carbon source

Glycerol is an interesting alternative carbon source in industrial bioprocesses due to its higher degree of reduction per carbon atom compared to sugars. During the last few years, significant progress has been made in improving the well-known industrial platform organism Saccharomyces cerevisiae with regard to its glycerol utilization capability, particularly in synthetic medium. This provided a basis for future metabolic engineering focusing on the production of valuable chemicals from glycerol. However, profound knowledge about the central carbon catabolism in synthetic glycerol medium is a prerequisite for such incentives. As a matter of fact, the current assumptions about the actual in vivo fluxes active on glycerol as the sole carbon source have mainly been based on omics data collected in complex media or were even deduced from studies with other non-fermentable carbon sources, such as ethanol or acetate. A number of uncertainties have been identified which particularly regard the role of the glyoxylate cycle, the subcellular localization of the respective enzymes, the contributions of mitochondrial transporters and the active anaplerotic reactions under these conditions. The review scrutinizes the current knowledge, highlights the necessity to collect novel experimental data using cells growing in synthetic glycerol medium and summarizes the current state of the art with regard to the production of valuable fermentation products from a carbon source that has been considered so far as 'non-fermentable' for the yeast S. cerevisiae.