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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.