Journal
METABOLIC ENGINEERING
Volume 28, Issue -, Pages 8-18Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.ymben.2014.11.007
Keywords
Sequential control; Biosynthetic pathway; Metabolic engineering; Carotenoids
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Funding
- Natural Science Foundation of China [21176215, 21406196]
- Program for Zhejiang Leading Team of ST Innovation [2011R50007]
- Fundamental Research Funds for the Central Universities [2014QNA4025]
- Zhejiang Provincial Natural Science Foundation of China [LQ14B060005]
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Balanced utilization of metabolic intermediates and controllable expression of genes in biosynthetic pathways are key issues for the effective production of value-added chemicals in microbes. An inducer/repressor-free sequential control strategy regulated by glucose concentration in the growth environment was proposed to address these issues, and its efficiency was validated using heterologous beta-carotenoid biosynthesis in Saccharornyces cerevisiae as an example. Through sequential control of the downstream, upstream, and competitive pathways of farnesyl diphosphate (FPP), the crucial metabolic node in the biosynthesis of terpenoids, in a predetermined order, a carotenoid production of 1156 mg/L (20.79 mg/g DCW) was achieved by high-cell density fermentation. Quantitative PCR analysis of the regulated genes demonstrated that the transcription patterns were controlled in a sequential manner as expected. The inducer/repressor-free nature of this strategy offers a both practical and economically efficient approach to improved biosynthetic production of value-added chemicals. (C) 2014 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved.
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