RAPTOR-mediated autophagy promotes the accumulation of lipid and terpenoids in Schizochytrium sp. HX-308

Autophagy is a conserved cellular process for maintaining cellular homeostasis and regulating lipid accumulation. However, it is unclear whether there is an intrinsic connection between autophagy levels and docosahexaenoic acid (DHA) accumulation in oleaginous microorganisms Schizochytrium sp. This study investigated the dynamic response of autophagy levels and DHA accumulation of Schizochytrium sp. under nitrogen-limited and nitrogen-sufficient conditions. The critical role of autophagy regulation was further confirmed by treatment with 5 mM 3-methyladenine in Schizochytrium sp., which enhanced the final titers of DHA and lipid to 31.8 g/L and 64.2 g/L, respectively. The results demonstrated that inhibiting autophagy levels promoted DHA production in Schizochytrium sp. Furthermore, transcriptome analysis revealed that transcription levels of autophagy related gene RAPTOR (mTOR regulatory related protein) were upregulated by 72.4% at 120 h, respectively. Functional validation experiments revealed that RAPTOR overexpression increased the DHA titer by 23.5% to 30.1 g/L and simultaneously enhanced β-carotene production by 36.3% to 5.8 mg/L in Schizochytrium sp. Moreover, overexpressing RAPTOR gene in an engineered strain Yarrowia lipolytica boosted eicosapentaenoic acid (EPA) production by 58.3% to 108.1 mg/L. Overall, this study demonstrated the effectiveness of autophagy regulation in promoting the production of lipids and carotenoids in oleaginous microorganisms.