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Improving carotenoids production in yeast via adaptive laboratory evolution
Affiliation:1. Department of Medical Research, China Medical University Hospital, No. 91 Hsueh-Shih Road, Taichung 402, Taiwan;2. Biodiversity Research Center, Academia Sinica, 128 Academia Road, Sec. 2, Nankang, Taipei 115, Taiwan;3. Agricultural Biotechnology Research Center, Academia Sinica, 128 Academia Road, Sec. 2, Nankang, Taipei 115, Taiwan;4. Department of Life Sciences, National Chung Hsing University, No. 250, Kuo Kuang Rd, Taichung 402, Taiwan;1. Department of Chemical and Biomolecular Engineering, Metabolic Engineering and Systems Biology Laboratory, University of Delaware, Newark, DE 19716, USA;2. Department of Bioengineering, University of California, San Diego, CA 92093, USA;3. Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, 2800 Lyngby, Denmark;1. Laboratory of Synthetic Microbiology, School of Chemical Engineering & Technology, Tianjin University, Tianjin 300072, PR China;2. Key Laboratory of Systems Bioengineering, Ministry of Education of China, Tianjin 300072, PR China;3. Collaborative Innovation Center of Chemical Science & Engineering, Tianjin, PR China;4. Center for Biosafety Research and Strategy, Tianjin University, Tianjin, PR China;1. School of Minerals Processing and Bioengineering, Central South University, Changsha, China;2. South China Institute of Environmental Sciences, Guangzhou, China
Abstract: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 carotenoids production in an engineered Saccharomyces cerevisiae 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.
Keywords:Evolutionary engineering  Carotenoids  Selective pressure  Yeast  Adaptive evolution
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