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Rewiring metabolic network by chemical modulator based laboratory evolution doubles lipid production in Crypthecodinium cohnii
- Diao, Jinjin, Song, Xinyu, Cui, Jinyu, Liu, Liangsen, Shi, Mengliang, Wang, Fangzhong, Zhang, Weiwen
- Metabolic engineering 2019 v.51 pp. 88-98
- Crypthecodinium cohnii, biochemical pathways, biomass production, biosynthesis, carbon, docosahexaenoic acid, enzyme inhibitors, lipid content, microalgae, omega-3 fatty acids, protocols, selection pressure, sethoxydim, starch
- Dietary omega-3 long-chain polyunsaturated fatty acids docosahexaenoic acid (DHA, C22:6) can be synthesized in microalgae Crypthecodinium cohnii; however, its productivity is still low. Here, we established a new protocol termed as “chemical modulator based adaptive laboratory evolution” (CM-ALE) to enhance lipid and DHA productivity in C. cohnii. First, ACCase inhibitor sethoxydim based CM-ALE was applied to redirect carbon equivalents from starch to lipid. Second, CM-ALE using growth modulator sesamol as selection pressure was conducted to relive negative effects of sesamol on lipid biosynthesis in C. cohnii, which allows enhancement of biomass productivity by 30% without decreasing lipid content when sesamol was added. After two-step CM-ALE, the lipid and DHA productivity in C. cohnii was respectively doubled to a level of 0.046 g/L/h and 0.025 g/L/h in culture with addition of 1 mM sesamol, demonstrating that this two-step CM-ALE could be a valuable approach to maximize the properties of microalgae.