Critical steps in carbon metabolism affecting lipid accumulation and their regulation in oleaginous microorganisms

Oleaginous microorganisms are able to convert numerous agro-industrial and municipal wastes into storage lipids (single cell oil (SCO)) and are therefore considered as potential biofuel producers. While from an environmental and technological point of view the idea to convert waste materials into fuels is very attractive, the production cost of SCO is not currently competitive to that of conventional oils due to the low productivity of oleaginous microorganisms in combination with the high fermentation cost. Current strategies used to optimize the lipid-accumulating capacity of oleaginous microorganisms include the overexpression of genes encoding for key enzymes implicated in fatty acid and triacylglycerol synthesis, such as ATP-dependent citrate lyase, acetyl-CoA carboxylase, malic enzyme, proteins of the fatty acid synthase complex, glycerol 3-phosphate dehydrogenase and various acyltransferases, and/or the inactivation of genes encoding for enzymes implicated in storage lipid catabolism, such as lipases and acyl-CoA oxidases. Furthermore, blocking, even partially, pathways competitive to lipid biosynthesis (e.g., those involved in the accumulation of storage polysaccharide or organic acid and polyol excretion) can also increase lipid-accumulating ability in oleaginous microorganisms. Methodologies, such as adaptive laboratory evolution, can be included in existing workflows for the generation of strains with improved lipid accumulation capacity. In our opinion, efforts should be focused in the construction of strains with high carbon uptake rates and a reprogrammed coordination of the individual parts of the oleaginous machinery that maximizes carbon flux towards lipogenesis.