title: Improving the production of acetyl-CoA-derived chemicals in Escherichia coli BL21(DE3) through iclR and arcA deletion.
abstract: Acetyl-CoA-derived chemicals are suitable for multiple applications in many industries. The bio-production of these chemicals has become imperative owing to the economic and environmental problems. However, acetate overflow is the major drawback for acetyl-CoA-derived chemicals production. Approaches for overcoming acetate overflow may be beneficial for the production of acetyl-CoA-derived chemicals.
  
  
  
  In this study, a transcriptional regulator iclR was knocked out in E.coli BL21(DE3) to overcome acetate overflow and improve the chemicals production. Two important acetyl-CoA-derived chemicals, phloroglucinol (PG) and 3-hydroxypropionate (3HP) were used to evaluate it. It is revealed that knockout of iclR significantly increased expressions of aceBAK operon. The cell yields and glucose utilization efficiencies were higher than those of control strains. The acetate concentrations were decreased by more than 50% and the productions of PG and 3HP were increased more than twice in iclR mutants. The effects of iclR knockout on cell physiology, cell metabolism and production of acetyl-CoA-derived chemicals were similar to those of arcA knockout in our previous study. However, the arcA-iclR double mutants couldn't gain higher productions of PG and 3HP. The mechanisms are unclear and needed to be resolved in future.
  
  
  
  Knockout of iclR significantly increased gene expression of aceBAK operon and concomitantly activated glyoxylate pathway. This genetic modification may be a good way to overcome acetate overflow, and improve the production of a wide range of acetyl-CoA-derived chemicals.
authors.affiliation: CAS Key Laboratory of Biobased Materials, Qingdao Institute of Bioenergy and Bioprocess Technology, Chinese Academy of Sciences, Qingdao, 266101, China.
authors.forename: Min
authors.initials: M
authors.lastname: Liu
authors.affiliation: Institute of Oceanology, Chinese Academy of Sciences, Qingdao, 266071, China.
authors.forename: Yamei
authors.initials: Y
authors.lastname: Ding
authors.affiliation: CAS Key Laboratory of Biobased Materials, Qingdao Institute of Bioenergy and Bioprocess Technology, Chinese Academy of Sciences, Qingdao, 266101, China.|University of Chinese Academy of Sciences, Beijing, 100049, China.
authors.forename: Hailin
authors.initials: H
authors.lastname: Chen
authors.affiliation: CAS Key Laboratory of Biobased Materials, Qingdao Institute of Bioenergy and Bioprocess Technology, Chinese Academy of Sciences, Qingdao, 266101, China.|University of Chinese Academy of Sciences, Beijing, 100049, China.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Zhao
authors.affiliation: CAS Key Laboratory of Biobased Materials, Qingdao Institute of Bioenergy and Bioprocess Technology, Chinese Academy of Sciences, Qingdao, 266101, China.
authors.forename: Huizhou
authors.initials: H
authors.lastname: Liu
authors.affiliation: CAS Key Laboratory of Biobased Materials, Qingdao Institute of Bioenergy and Bioprocess Technology, Chinese Academy of Sciences, Qingdao, 266101, China. xianmo1@qibebt.ac.cn.
authors.forename: Mo
authors.initials: M
authors.lastname: Xian
authors.affiliation: CAS Key Laboratory of Biobased Materials, Qingdao Institute of Bioenergy and Bioprocess Technology, Chinese Academy of Sciences, Qingdao, 266101, China. zhaoguang@qibebt.ac.cn.|Randian Technology Company Limited, Tianjin, 300457, China. zhaoguang@qibebt.ac.cn.
authors.forename: Guang
authors.initials: G
authors.lastname: Zhao
mesh_terms: D000085:Acetates / Q000378:metabolism; D000105:Acetyl Coenzyme A / Q000096:biosynthesis / Q000378:metabolism*; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics*; D004926:Escherichia coli / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism* / Q000502:physiology; D029968:Escherichia coli Proteins / Q000235:genetics*; D015964:Gene Expression Regulation, Bacterial; D055786:Gene Knockout Techniques; D005947:Glucose / Q000378:metabolism; D006038:Glyoxylates / Q000378:metabolism; D019344:Lactic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D053858:Metabolic Networks and Pathways / Q000235:genetics; D009876:Operon; D010696:Phloroglucinol / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics*; D017384:Sequence Deletion / Q000235:genetics*
chemical_list: D000085:Acetates; D001425:Bacterial Outer Membrane Proteins; D029968:Escherichia coli Proteins; D006038:Glyoxylates; D012097:Repressor Proteins; C041610:arcA protein, E coli; C067479:IclR protein, E coli; D019344:Lactic Acid; D000105:Acetyl Coenzyme A; C031601:hydracrylic acid; D010696:Phloroglucinol; D005947:Glucose; C031150:glyoxylic acid
keywords: 3-hydroxypropionate; Acetyl-CoA; Escherichia coli; Phloroglucinol; arcA; iclR