Metabolic engineering of Escherichia coli to produce a monophosphoryl lipid A adjuvant

Yuhyun Ji, Jinsu An, Dohyeon Hwang, Da Hui Ha, Sang Min Lim, Chankyu Lee, Jinshi Zhao, Hyun Kyu Song, Eun Gyeong Yang, Pei Zhou, Hak Suk Chung

Research output: Contribution to journalArticle

Abstract

Monophosphoryl lipid A (MPLA) species, including MPL (a trade name of GlaxoSmithKline) and GLA (a trade name of Immune Design, a subsidiary of Merck), are widely used as an adjuvant in vaccines, allergy drugs, and immunotherapy to boost the immune response. Even though MPLA is a derivative of lipopolysaccharide (LPS), a component of the outer membrane of Gram-negative bacteria, bacterial strains producing MPLA have not been found in nature nor engineered. In fact, MPLA generation involves expensive and laborious procedures based on synthetic routes or chemical transformation of precursors isolated from Gram-negative bacteria. Here, we report the engineering of an Escherichia coli strain for in situ production and accumulation of MPLA. Furthermore, we establish a succinct method for purifying MPLA from the engineered E. coli strain. We show that the purified MPLA (named EcML) stimulates the mouse immune system to generate antigen-specific IgG antibodies similarly to commercially available MPLA, but with a dramatically reduced manufacturing time and cost. Our system, employing the first engineered E. coli strain that directly produces the adjuvant EcML, could transform the current standard of industrial MPLA production.

Original languageEnglish
Pages (from-to)193-202
Number of pages10
JournalMetabolic engineering
Volume57
DOIs
Publication statusPublished - 2020 Jan 1

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Keywords

  • Adjuvant
  • Gram-negative bacterial outer membrane
  • Lipid A 1-phosphatase
  • Lipopolysaccharide biosynthesis
  • Monophosphoryl lipid A
  • Vaccine adjuvant

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Applied Microbiology and Biotechnology

Cite this

Ji, Y., An, J., Hwang, D., Ha, D. H., Lim, S. M., Lee, C., Zhao, J., Song, H. K., Yang, E. G., Zhou, P., & Chung, H. S. (2020). Metabolic engineering of Escherichia coli to produce a monophosphoryl lipid A adjuvant. Metabolic engineering, 57, 193-202. https://doi.org/10.1016/j.ymben.2019.11.009