title: Increasing Malonyl-CoA Derived Product through Controlling the Transcription Regulators of Phospholipid Synthesis in Saccharomyces cerevisiae.
abstract: Malonyl-CoA is a precursor of a variety of compounds such as polyketides and flavonoids. In Saccharomyces cerevisiae, malonyl-CoA concentration is tightly regulated and therefore maintained at a very low level, limiting the production of malonyl-CoA-derived chemicals. Here we manipulated the phospholipid synthesis transcriptional regulators to control the malonyl-CoA levels and increase the downstream product. Through manipulating different regulators including Ino2p, Ino4p, Opi1p, and a series of synthetic Ino2p variants, combining with studying the inositol and choline effect, the engineered strain achieved a 9-fold increase of the titer of malonyl-CoA-derived product 3-hydroxypropionic acid, which is among the highest improvement relative to previously reported strategies. Our study provides a new strategy to regulate malonyl-CoA availability and will contribute to the production of other highly valued malonyl-CoA-derived chemicals.
authors.affiliation: State Key Laboratory of Microbial Technology, School of Life Science, Shandong University , Jinan 250100, China.
authors.forename: Xiaoxu
authors.initials: X
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Microbial Technology, School of Life Science, Shandong University , Jinan 250100, China.
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Microbial Technology, School of Life Science, Shandong University , Jinan 250100, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Shen
authors.affiliation: State Key Laboratory of Microbial Technology, School of Life Science, Shandong University , Jinan 250100, China.
authors.forename: Jin
authors.identifier: 0000-0001-6789-6057
authors.initials: J
authors.lastname: Hou
authors.affiliation: State Key Laboratory of Microbial Technology, School of Life Science, Shandong University , Jinan 250100, China.
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Bao
mesh_terms: D015966:Gene Expression Regulation, Fungal / Q000235:genetics / Q000502:physiology; D019344:Lactic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D008316:Malonyl Coenzyme A / Q000235:genetics / Q000378:metabolism*; D010743:Phospholipids / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D010743:Phospholipids; D029701:Saccharomyces cerevisiae Proteins; D019344:Lactic Acid; D008316:Malonyl Coenzyme A; C031601:hydracrylic acid
keywords: 3-hydroxypropionic acid; INO2; INO4; Saccharomyces cerevisiae; malonyl-CoA