Abstract
Adaptive laboratory evolution (ALE) was commonly used for strain improvement. Crypthecodinium cohnii is known to accumulate lipids with a high fraction of docosahexaenoic acid (DHA). In order to improve DHA production under high substrate concentration, a glucose-tolerant C. cohnii strain was firstly obtained by ALE after 260 cycles for 650days with gradually increased glucose concentration. The results of lipids content showed that DHA-rich lipids accumulation in the evolved strain could increase by 15.49% at 45g/L glucose concentrations. To reveal mechanisms related to glucose tolerance of C. cohnii through ALE, metabolic profiles were then compared and the results showed that hub metabolites including glycerol, glutamic acid, malonic acid and succinic acid were positively regulated during ALE. The study demonstrated that metabolomic analysis complemented with ALE could be an effective and valuable strategy for basic mechanisms of molecular evolution and adaptive changes in C. cohnii.
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