Improving carotenoids production in yeast via adaptive laboratory evolution

Adaptive laboratory evolution is an important tool for the engineering of strains for industrially relevant phenotypes. Traditionally, adaptive laboratory evolution has been implemented to improve robustness of industrial strains under diverse operational conditions; however due to the required coupling between growth and survival, its application for increased production of secondary metabolites generally results in decreased production due to the metabolic burden imposed by, or toxicity of, the produced compound. In this study, adaptive laboratory evolution was successfully applied to improve carotenoicls production in an engineered Saccharornyces cerevisine producer strain by exploiting the antioxidant properties of carotenoids. Short-term evolution experiment using periodic hydrogen peroxide shocking schemes resulted in a 3-fold increase in carotenoids production (from 6 mg/g dry cell weight to up to 18 mg/g dry cell weight). Subsequent transcriptome analysis was used to elucidate the molecular mechanisms for increased carotenoids production. Upregulation of genes related with lipid biosynthesis and mevalonate biosynthesis pathways were commonly observed in the carotenoids hyper-producers analyzed. (C) 2013 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved.