Metabolic switch points enabling targeted lipid accumulation in oleaginous and non-oleaginous yeasts: A comparative review

Oleaginicity is a unique property exhibited by only a few organisms to store the excess carbon in the form of lipids under exceptional circumstances. This property is regulated by an intricate interplay of cellular metabolism and external environmental/culture parameters. This review highlights the mechanism at cellular level that divert the carbon flux toward lipid accumulation in oleaginous yeast/fungi and compares these to their ethanol synthesizing counterparts. Reported information on the influence of culture conditions, media and stress factors on lipogenesis and lipid accumulation have been investigated considering the intricate interplay among various metabolic pathways. The contribution of reductants, enzymatic manoeuvring of carbon flux, roles of carriers/transporters, transcription regulators along with other key cytosolic or mitochondrial enzymes for lipid synthesis and accumulation have been investigated to understand the differential behaviour of oleaginous and ethanologenic yeast. The switch points that differentiate oleaginous and non-oleaginous yeast strains, e.g. Crabtree vs non-Crabtree metabolism, NADPH source, Nitrogen-triggered TOR/SNF1 signalling, ACL-dependent acetyl-CoA supply, have been reviewed. Although the roles of key enzymes such as malate enzyme (ME) and ATP: citrate lyase (ACL) and variations in carbon/nitrogen ratios of the culture medium have been critically reviewed before, the oleaginous behaviour in yeast in comparison with ethanologenic yeast and the mechanistic switch points involved are being reviewed here. The review provides a foundation for innovative research designs for directing the abundant acetyl-CoA flux of oleaginous yeast via intelligent strain/media design, for large-scale industrial applications, by using the information on switch points and metabolic interplay of pathways. • Oleaginous yeast diverts C flux for lipid synthesis, unlike non oleaginous strains. • External parameters and interplay of metabolic pathways facilitate lipogenesis. • Carriers, transcription regulators, pathway modulators regulate oleaginicity.