Overproduction of docosahexaenoic acid in Schizochytrium sp. through genetic engineering of oxidative stress defense pathways

通过氧化应激防御途径的基因工程,在裂殖壶菌中过量生产二十二碳六烯酸

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作者:Xiao Han, Zhaohui Li, Ying Wen, Zhi Chen

Background

Oxidation and peroxidation of lipids in microorganisms result in increased levels of intracellular reactive oxygen species (ROS) and reactive aldehydes, and consequent reduction of cell growth and lipid accumulation.

Conclusions

Our findings demonstrate that engineering of oxidative stress defense pathways is an effective strategy for promoting cell robustness, lipid yield, and DHA production in Schizochytrium.

Results

To reduce oxygen-mediated cell damage and increase lipid and docosahexaenoic acid (DHA) production in Schizochytrium sp., we strengthened the oxidative stress defense pathways. Overexpression of the enzymes thioredoxin reductase (TRXR), aldehyde dehydrogenase (ALDH), glutathione peroxidase (GPO), and glucose-6-phosphate dehydrogenase (ZWF) strongly promoted cell growth, lipid yield, and DHA production. Coexpression of ZWF, ALDH, GPO, and TRXR enhanced ROS-scavenging ability. Highest values of dry cell weight, lipid yield, and DHA production (50.5 g/L, 33.1 g/L, and 13.3 g/L, respectively) were attained in engineered strain OaldH-gpo-trxR by shake flask fed-batch culture; these were increases of 18.5%, 80.9%, and 114.5% relative to WT values. Conclusions: Our findings demonstrate that engineering of oxidative stress defense pathways is an effective strategy for promoting cell robustness, lipid yield, and DHA production in Schizochytrium.

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