NADP+-dependent isocitrate dehydrogenase as a novel target for altering carbon flux to lipid accumulation and enhancing antioxidant capacity in Tetradesmus obliquus

[Display omitted] •A mitochondrial transgenic isocitrate dehydrogenase (ToIDH) was identified, enhancing NADPH synthesis and subsequent lipid accumulation in cells.•ToIDH significantly elevated lipid hyperaccumulation and reallocated the cellular carbon flux.•The introduction of ToIDH modified the f...

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Published in:Bioresource technology 2024-03, Vol.395, p.130365-130365, Article 130365
Main Authors: Li, Jing, Wang, Wei, Li, Bingze, Xue, Yunzhuan, Wang, Xinxin, Liu, Shihui, Hu, Shuwei, Tang, Jiaxuan, Yan, Bo, Li, Tong, Xue, Jiao
Format: Article
Language:English
Subjects:
Antioxidant capacity
Antioxidants
Carbon
Fatty Acids
Isocitrate dehydrogenase
Isocitrate Dehydrogenase - genetics
Isocitrate Dehydrogenase - metabolism
NADP - metabolism
NADPH
NADPH Dehydrogenase
Tetradesmus obliquus
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Summary:[Display omitted] •A mitochondrial transgenic isocitrate dehydrogenase (ToIDH) was identified, enhancing NADPH synthesis and subsequent lipid accumulation in cells.•ToIDH significantly elevated lipid hyperaccumulation and reallocated the cellular carbon flux.•The introduction of ToIDH modified the fatty acid profile and improved the antioxidant capacity of the cells.•Under salt stress, lipid accumulation was further augmented in the ToIDH-overexpressed algal strain, albeit at a considerable cost to the growth rate. Regulatory complexities in lipogenesis hinder the harmonization of metabolic carbon precursors towards lipid synthesis. Exploring regulatory complexities in lipogenesis, this study identifies NADP+-dependent isocitrate dehydrogenase (IDH) in Tetradesmus obliquus as a key factor. Overexpression IDH in strains ToIDH-1 and ToIDH-2 resulted in a 1.69 and 1.64-fold increase in neutral lipids, respectively, compared to the wild type, with lipid yield reaching 234.56 and 227.17 mg/L. Notably, despite slower growth, the cellular biomass augmented to 790.67 mg/L. Metabolite analysis indicated a shift in carbon precursors from protein to lipid and carbohydrate synthesis. Morphological observations revealed increases in the volume and number of lipid droplets, alongside a change in the fatty acid profile favoring monounsaturated and saturated fatty acids. Furthermore, IDH overexpression enhanced NADPH production and antioxidant activity, thereby further boosting lipid accumulation when combined with salt stress. This study suggests a pathway for improved lipogenesis and algal growth via metabolic engineering.
ISSN:0960-8524
1873-2976
DOI:10.1016/j.biortech.2024.130365