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

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. 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.

Automated summary

Enhancing oxidative stress defense pathways through overexpression of TRXR, ALDH, GPO, and ZWF enzymes promotes cell growth, lipid yield, and DHA production in Schizochytrium sp. The engineered strain OaldH-gpo-trxR achieved significantly higher values for dry cell weight, lipid yield, and DHA production compared to the wild type strain. The findings demonstrate the effectiveness of engineering oxidative stress defense pathways in promoting lipid yield and DHA production in Schizochytrium.