Zhao Yuetong, Zhu Xingyu, Riaz Nimra, Liu Xiuping, Li Jiaqian, Wang Guangyi
Center of Marine Environmental Ecology, School of Environmental Science and Engineering, Tianjin University, Tianjin 300072, China.
Key Laboratory of Systems Bioengineering (Ministry of Education), Tianjin University, Tianjin 300072, China.
Mar Drugs. 2025 Aug 30;23(9):354. doi: 10.3390/md23090354.
Salinity is a key environmental factor regulating lipid metabolism in marine oleaginous protists. This study examined the impact of NaCl concentration on growth, glucose utilization, and lipid biosynthesis in sp. ATCC 26185. Moderate salinity (20 g/L) enhanced biomass and glucose uptake, while high salinity (45 g/L) induced osmotic stress yet significantly promoted squalene accumulation (17.27 mg/g), a 3.26-fold increase compared with 0 g/L NaCl (5.29 mg/g). Integrated transcriptomic and metabolomic analyses revealed that salinity-dependent activation of glycolysis, the TCA cycle, and the pentose phosphate pathway increased cellular ATP, NADH, and NADPH levels. Under salt stress, the mevalonate (MVA) pathway was transcriptionally upregulated, with key enzymes, including ACAT, HMGR, and IDI, showing marked induction, which supports enhanced carbon flux toward squalene biosynthesis. Despite SQS downregulation, squalene accumulation increased, likely due to elevated precursor availability and reduced flux to downstream sterol pathways. Concurrently, high salinity repressed expression of ACC, FAS-α, and FAS-β, reducing saturated fatty acid levels, while upregulation of PKSB-favored polyunsaturated fatty acid (PUFA) synthesis. These findings suggest that high-salt stress triggers transcriptional reprogramming, redirecting acetyl-CoA from fatty acid synthesis toward squalene and PUFA production. This study offers new insights into the metabolic plasticity of thraustochytrids and highlights salinity modulation as a promising strategy for enhancing high-value lipid yields in marine biotechnology.
盐度是调节海洋产油原生生物脂质代谢的关键环境因素。本研究考察了NaCl浓度对 sp. ATCC 26185生长、葡萄糖利用和脂质生物合成的影响。适度盐度（20 g/L）提高了生物量和葡萄糖摄取量，而高盐度（45 g/L）虽诱导渗透胁迫，但显著促进了角鲨烯积累（17.27 mg/g），与0 g/L NaCl（5.29 mg/g）相比增加了3.26倍。综合转录组学和代谢组学分析表明，糖酵解、三羧酸循环和磷酸戊糖途径的盐度依赖性激活增加了细胞ATP、NADH和NADPH水平。在盐胁迫下，甲羟戊酸（MVA）途径转录上调，包括ACAT、HMGR和IDI在内的关键酶显著诱导，这支持了碳通量增强以合成角鲨烯。尽管鲨烯合酶（SQS）下调，但角鲨烯积累增加，可能是由于前体可用性提高以及向下游甾醇途径的通量减少。同时，高盐度抑制了ACC、FAS-α和FAS-β的表达，降低了饱和脂肪酸水平，而PKSB的上调有利于多不饱和脂肪酸（PUFA）合成。这些发现表明，高盐胁迫触发转录重编程，将乙酰辅酶A从脂肪酸合成转向角鲨烯和PUFA生产。本研究为破囊壶菌的代谢可塑性提供了新见解，并突出了盐度调节作为提高海洋生物技术中高价值脂质产量的一种有前景的策略。
