Skip to main content

Deletion of arcA increased the production of acetyl-CoA-derived chemicals in recombinant Escherichia coli

An Erratum to this article was published on 01 March 2016



Acetyl-CoA is used to produce many valuable metabolites in Escherichia coli. However, acetate overflow is a major shortcoming. Knockout of the global regulator gene, arcA, may solve this problem.


The arcA gene of E. coli BL21(DE3) was knocked out, and the production of phloroglucinol (PG) and 3-hydroxypropionate (3HP), both derived from acetyl-CoA, were used to evaluate its effect. The arcA mutants had higher cell yields and higher glucose utilization efficiencies than the corresponding control strains, and the productions of PG and 3HP were 0.92 g/l and 0.27 g/l, respectively; more than twice that of the control strains. Furthermore, arcA knockout also showed significant repression on formation of acetate, the major byproduct in fermentation. Acetate concentrations were decreased 69.4 % and 87 % by arcA knockout during the production of PG and 3HP, respectively.


The arcA gene knockout is a solution to acetate overflow and may improve production of a wide range of acetyl-CoA-derived metabolites.

This is a preview of subscription content, access via your institution.

Fig. 1
Fig. 2


  • Cao Y, Jiang X, Zhang R, Xian M (2011) Improved phloroglucinol production by metabolically engineered Escherichia coli. Appl Microbiol Biotechnol 9:1545–1552

    Article  Google Scholar 

  • Chen Y, Daviet L, Schalk M, Siewers V, Nielsen J (2013) Establishing a platform cell factory through engineering of yeast acetyl-CoA metabolism. Metab Eng 15:48–54

    CAS  Article  PubMed  Google Scholar 

  • Edwards RAKL, Schifferli DM (1998) Improved allelic exchange vectors and their use to analyze 987P fimbria gene expression. Gene 207:149–157

    CAS  Article  PubMed  Google Scholar 

  • Farmer WR, Liao JC (1997) Reduction of aerobic acetate production by Escherichia coli. Applied and Environmental microbiology 63(8):3205–3210

    CAS  PubMed  PubMed Central  Google Scholar 

  • Kang Z, Geng Y, Xia Y, Kang J, Qi Q (2009) Engineering Escherichia coli for an efficient aerobic fermentation platform. J Biotechnol 144:58–63

    CAS  Article  PubMed  Google Scholar 

  • Kim HJ, Hou BK, Lee SG, Kim JS, Lee DW, Lee SJ (2013) Genome-wide analysis of redox reactions reveals metabolic engineering targets for D-lactate overproduction in Escherichia coli. Metab Eng 18:44–52

    CAS  Article  PubMed  Google Scholar 

  • Liu C, Wang Q, Xian M, Ding Y, Zhao G (2013) Dissection of malonyl-coenzyme a reductase of Chloroflexus aurantiacus results in enzyme activity improvement. PLoS One 8:e75554

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  • Lynch AS, Lin E (1996) Transcriptional control mediated by the ArcA two-component response regulator protein of Escherichia coli: characterization of DNA binding at target promoters. J Bacteriol 178:6238–6249

    CAS  PubMed  PubMed Central  Google Scholar 

  • Nikel PI, Pettinari MJ, Ramírez MC, Galvagno MA, Méndez BS (2008) Escherichia coli arcA mutants: metabolic profile characterization of microaerobic cultures using glycerol as a carbon source. J Mol Microbiol Biotechnol 15:48–54

    CAS  Article  PubMed  Google Scholar 

  • Nizam SA, Zhu J, Ho PY, Shimizu K (2009) Effects of arcA and arcB genes knockout on the metabolism in Escherichia coli under aerobic condition. Biochem Eng J 44:240–250

    CAS  Article  Google Scholar 

  • Perrenoud A, Sauer U (2005) Impact of global transcriptional regulation by ArcA, ArcB, Cra, Crp, Cya, Fnr, and Mlc on glucose catabolism in Escherichia coli. J Bacteriol 187:3171–3179

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  • Rathnasingh C, Raj SM, Jo JE, Park S (2009) Development and evaluation of efficient recombinant Escherichia coli strains for the production of 3-hydroxypropionic acid from glycerol. Biotechnol Bioeng 104:729–739

    CAS  PubMed  Google Scholar 

  • Rathnasingh C, Raj SM, Lee Y, Catherine C, Ashok S, Park S (2012) Production of 3-hydroxypropionic acid via malonyl-CoA pathway using recombinant Escherichia coli strains. J Biotechnol 157:633–640

    CAS  Article  PubMed  Google Scholar 

  • Singh IP, Sidana J, Bansal P, Foley WJ (2009) Phloroglucinol compounds of therapeutic interest: global patent and technology status. Expert Opin 19:847–866

    CAS  Google Scholar 

  • Vemuri GN, Eiteman MA, Altman E (2006) Increased recombinant protein production in Escherichia coli strains with overexpressed water-forming NADH oxidase and a deleted ArcA regulatory protein. Biotechnol Bioeng 94:538–542

    CAS  Article  PubMed  Google Scholar 

  • Waegeman H, Maertens J, Beauprez J, De Mey M, Soetaert W (2012) Effect of iclR and arcA deletions on physiology and metabolic fluxes in Escherichia coli BL21 (DE3). Biotechnol Lett 34:329–337

    CAS  Article  PubMed  Google Scholar 

  • Wong MS, Wu S, Causey TB, Bennett GN, San KY (2008) Reduction of acetate accumulation in Escherichia coli cultures for increased recombinant protein production. Metab Eng 10:97–108

    CAS  Article  PubMed  Google Scholar 

  • Zha W, Rubin-Pitel SB, Zhao H (2008) Exploiting genetic diversity by directed evolution: molecular breeding of type III polyketide synthases improves productivity. Mol BioSyst 4:246–248

    CAS  Article  PubMed  Google Scholar 

Download references


This work was supported by100-Talent Project of CAS (to GZ), Natural Science Foundation of Shandong Province (ZR2013EMZ002), National Natural Science Foundation of China (21376255), Taishan Scholars Climbing Program of Shandong(No.tspd20150210)and Key Program of CAS (KGZD-EW-606-1-3).

Author information

Authors and Affiliations


Corresponding authors

Correspondence to Huizhou Liu or Gao Zhao.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Liu, M., Yao, L., Xian, M. et al. Deletion of arcA increased the production of acetyl-CoA-derived chemicals in recombinant Escherichia coli . Biotechnol Lett 38, 97–101 (2016).

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI:


  • Acetate-derived metabolites
  • Acetyl-CoA
  • arcA
  • Escherichia coli
  • 3-Hydroxypropionate
  • Phloroglucinol