PMID- 37079130 OWN - NLM STAT- MEDLINE DCOM- 20230505 LR - 20230505 IS - 1615-7605 (Electronic) IS - 1615-7591 (Linking) VI - 46 IP - 6 DP - 2023 Jun TI - Metabolic analysis of Schizochytrium sp. mutants with high EPA content achieved with ARTP mutagenesis screening. PG - 893-901 LID - 10.1007/s00449-023-02874-5 [doi] AB - Eicosapentaenoic acid (EPA) belonged to the omega-3 series of polyunsaturated fatty acids and had physiological functions lipid as regulating blood lipid and preventing cardiovascular diseases. Schizochytrium sp. was considered to be a potential industrial fermentation strain of EPA because of its fast growth, high oil content, and simple fatty acid composition. However, Schizochytrium sp. produced EPA with low production efficiency and a long synthesis path. This research aims to improve the yield of EPA in Schizochytrium sp. by ARTP mutagenesis and to reveal the mechanism of high-yield EPA through transcriptome analysis. ARTP mutagenesis screening yielded the mutant M12 that whereas the productivity of EPA increased 108% reaching 0.48 g/L, the total fatty acid concentration was 13.82 g/L with an increase of 13.7%. The transcriptomics revealed 2995 differentially expressed genes were identified between M12 and the wild-type strain and transcripts involved in carbohydrate, amino acid, energy, and lipid metabolism were up-regulated. Among them, the hexokinase (HK) and the phosphofructokinase genes (PFK), which can catalyze pyruvate to acetyl-CoA, were increased 2.23-fold and 1.78-fold. Glucose-6-phosphate dehydrogenase (G6PD) and glutamate dehydrogenase (GLDH), which can both generate NADPH, were increased by 1.67-fold and 3.11-fold. Furthermore, in the EPA synthesis module, the expression of 3-oxoacyl-[acyl-carrier protein] reductase(fabG) and carbonyl reductase 4 / 3-oxoacyl-[acyl-carrier protein] reductase beta subunit(CBR4), also up-regulated 1.11-fold and 2.67-fold. These may lead to increases in cell growth. The results provide an important reference for further research on promoting fatty acid and EPA accumulation in Schizochytrium sp. CI - (c) 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature. FAU - Wei, Xinyu AU - Wei X AD - School of Food Science and Pharmaceutical Engineering, Nanjing Normal University, Nanjing, 210023, People's Republic of China. FAU - Wang, Yuzhou AU - Wang Y AD - School of Food Science and Pharmaceutical Engineering, Nanjing Normal University, Nanjing, 210023, People's Republic of China. FAU - Liu, Xiner AU - Liu X AD - School of Food Science and Pharmaceutical Engineering, Nanjing Normal University, Nanjing, 210023, People's Republic of China. FAU - Hu, Zijian AU - Hu Z AD - School of Food Science and Pharmaceutical Engineering, Nanjing Normal University, Nanjing, 210023, People's Republic of China. FAU - Qian, Jinyi AU - Qian J AD - School of Food Science and Pharmaceutical Engineering, Nanjing Normal University, Nanjing, 210023, People's Republic of China. FAU - Shi, Tianqiong AU - Shi T AD - School of Food Science and Pharmaceutical Engineering, Nanjing Normal University, Nanjing, 210023, People's Republic of China. FAU - Wang, Yuetong AU - Wang Y AD - School of Food Science and Pharmaceutical Engineering, Nanjing Normal University, Nanjing, 210023, People's Republic of China. FAU - Ye, Chao AU - Ye C AD - School of Food Science and Pharmaceutical Engineering, Nanjing Normal University, Nanjing, 210023, People's Republic of China. chaoye09@njnu.edu.cn. LA - eng GR - 22208167/National Natural Science Foundation of China/ PT - Journal Article DEP - 20230420 PL - Germany TA - Bioprocess Biosyst Eng JT - Bioprocess and biosystems engineering JID - 101088505 RN - AAN7QOV9EA (Eicosapentaenoic Acid) RN - 25167-62-8 (Docosahexaenoic Acids) RN - 0 (Fatty Acids) RN - EC 1.- (Oxidoreductases) RN - 0 (Carrier Proteins) SB - IM MH - *Eicosapentaenoic Acid/metabolism MH - Docosahexaenoic Acids/metabolism MH - *Stramenopiles MH - Fatty Acids/metabolism MH - Mutagenesis MH - Oxidoreductases/metabolism MH - Carrier Proteins/genetics OTO - NOTNLM OT - ARTP OT - EPA OT - Schizochytrium sp. OT - Transcriptome EDAT- 2023/04/20 13:41 MHDA- 2023/05/05 06:42 CRDT- 2023/04/20 11:17 PHST- 2023/01/17 00:00 [received] PHST- 2023/04/10 00:00 [accepted] PHST- 2023/05/05 06:42 [medline] PHST- 2023/04/20 13:41 [pubmed] PHST- 2023/04/20 11:17 [entrez] AID - 10.1007/s00449-023-02874-5 [pii] AID - 10.1007/s00449-023-02874-5 [doi] PST - ppublish SO - Bioprocess Biosyst Eng. 2023 Jun;46(6):893-901. doi: 10.1007/s00449-023-02874-5. Epub 2023 Apr 20.