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

• Main Authors: Chen, Z. (Author), Han, X. (Author), Li, Z. (Author), Wen, Y. (Author)
• Format: Article
• Language: English
• Published: BioMed Central Ltd 2021
• Subjects: accumulation; Aldehyde dehydrogenase; Aldehydes; Batch cell culture; Cell engineering; Cell growth; Cell proliferation; Cells; cyanobacterium; defense behavior; Docosahexaenoic acid; fatty acid; Fed-batch cultures; gene expression; genetic engineering; Genetic engineering; Glucose-6-phosphate dehydrogenase; Glutathione peroxidase; Growth kinetics; growth rate; lipid; Lipid accumulations; Network security; oxidative stress; Oxidative stress; Oxidative stress defense pathway; Oxygen; reactive oxygen species; Scavenging ability; Schizochytrium; Schizochytrium sp; Thioredoxin reductase; Unsaturated fatty acids
• Online Access: View Fulltext in Publisher

 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. © 2021, The Author(s).