Developing Gram-negative bacteria for the secretion of heterologous proteins

Lisa Ann Burdette, Samuel Alexander Leach, Han Teng Wong, Danielle Tullman-Ercek*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

76 Scopus citations


Gram-negative bacteria are attractive hosts for recombinant protein production because they are fast growing, easy to manipulate, and genetically stable in large cultures. However, the utility of these microbes would expand if they also could secrete the product at commercial scales. Secretion of biotechnologically relevant proteins into the extracellular medium increases product purity from cell culture, decreases downstream processing requirements, and reduces overall cost. Thus, researchers are devoting significant attention to engineering Gram-negative bacteria to secrete recombinant proteins to the extracellular medium. Secretion from these bacteria operates through highly specialized systems, which are able to translocate proteins from the cytosol to the extracellular medium in either one or two steps. Building on past successes, researchers continue to increase the secretion efficiency and titer through these systems in an effort to make them viable for industrial production. Efforts include modifying the secretion tags required for recombinant protein secretion, developing methods to screen or select rapidly for clones with higher titer or efficiency, and improving reliability and robustness of high titer secretion through genetic manipulations. An additional focus is the expression of secretion machineries from pathogenic bacteria in the "workhorse" of biotechnology, Escherichia coli, to reduce handling of pathogenic strains. This review will cover recent advances toward the development of high-expressing, high-secreting Gram-negative production strains.

Original languageEnglish (US)
Article number196
JournalMicrobial Cell Factories
Issue number1
StatePublished - Dec 20 2018


  • Bacterial secretion systems
  • Protein secretion
  • Recombinant protein

ASJC Scopus subject areas

  • Applied Microbiology and Biotechnology
  • Bioengineering
  • Biotechnology


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