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Extension of cell membrane boosting squalene production in the engineered Escherichia coli
Authors:Yunhe Meng  Xixi Shao  Yan Wang  Yumei Li  Xiaojian Zheng  Gongyuan Wei  Seon-Won Kim  Chonglong Wang
Institution:1. School of Biology and Basic Medical Sciences, Soochow University, Suzhou, China;2. Division of Applied Life Science (BK21 Plus), PMBBRC, Gyeongsang National University, Jinju, Republic of Korea
Abstract:Squalene is a lipophilic and non-volatile triterpene with many industrial applications for food, pharmaceuticals, and cosmetics. Metabolic engineering focused on optimization of the production pathway suffer from little success in improving titers because of a limited space of the cell membrane accommodating the lipophilic product. Extension of cell membrane would be a promising approach to overcome the storage limitation for successful production of squalene. In this study, Escherichia coli was engineered for squalene production by overexpression of some membrane proteins. The highest production of 612 mg/L was observed in the engineered E. coli with overexpression of Tsr, a serine chemoreceptor protein, which induced invagination of inner membrane to form multilayered structure. It was also observed an increase in unsaturated fatty acid in membrane lipids composition, suggesting cellular response to maintain membrane fluidity against squalene accumulation in the engineered strain. This study potentiates the capability of E. coli for squalene production and provides an effective strategy for the enhanced production of such compounds.
Keywords:Escherichia coli  membrane extension  metabolic engineering  mevalonate pathway  squalene
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