Utilizing lipidomics and fatty acid synthase inhibitors to explore lipid accumulation in two thraustochytrid species

Abstract

Thraustochytrids are marine protists with an excellent ability to produce health-beneficial docosahexaenoic acid (DHA)-rich lipids. Since the demand for DHA sources for food and feed is increasing, a deeper understanding of the potential to enhance the DHA-production in thraustochytrids is important for a sustainable DHA supply. In most thraustochytrids, including the strains used in this work, DHA is synthesized by a polyketide synthase-like pathway (PKS), and not through the common fatty acid synthetase (FAS) pathway. Both pathways use the same precursors. The aim of this study was to determine if inhibiting the production of fatty acids (FA) through the FAS pathway under nitrogen starvation would result in higher net DHA production rates measured as DHA content, and if the channeling of the synthesized fatty acids to different lipids species is similar in two different thraustochytrid strains. We found that the DHA production rates in Aurantiochytrium limacinum SR21 and Aurantiochytrium sp. T66 were not affected when treated with the FAS-inhibitor cerulenin, despite a reduction of FAS-derived FAs. This indicates that precursor availability is less likely to be the limiting factor for DHA synthesis. Still, cerulenin-treatment in the lipid accumulation phase resulted in higher concentrations of the triacylglycerol (TAG) TG(22:6/22:6/22:6) than in the untreated cells after three hours, demonstrating that FAS inhibition is a possible strategy to enhance the content of DHA-rich lipids. Moreover, the relatively high abundance of the diacylglycerol DG(22:6/22:6) suggests the presence of an obstacle for using DG(22:6/22:6) as substrate to synthesize DHA-rich TAGs, a step that potentially can be improved by metabolic engineering.