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

Publication ,  Journal Article
Ji, Y; An, J; Hwang, D; Ha, DH; Lim, SM; Lee, C; Zhao, J; Song, HK; Yang, EG; Zhou, P; Chung, HS
Published in: Metab Eng
January 2020

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.

Duke Scholars

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Published In

Metab Eng

DOI

EISSN

1096-7184

Publication Date

January 2020

Volume

57

Start / End Page

193 / 202

Location

Belgium

Related Subject Headings

  • Mice, Inbred BALB C
  • Mice
  • Metabolic Engineering
  • Lipid A
  • Immunoglobulin G
  • Escherichia coli
  • Biotechnology
  • Antibody Formation
  • Animals
  • Adjuvants, Immunologic
 

Citation

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Chicago
ICMJE
MLA
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Ji, Y., An, J., Hwang, D., Ha, D. H., Lim, S. M., Lee, C., … Chung, H. S. (2020). Metabolic engineering of Escherichia coli to produce a monophosphoryl lipid A adjuvant. Metab Eng, 57, 193–202. https://doi.org/10.1016/j.ymben.2019.11.009
Ji, Yuhyun, Jinsu An, Dohyeon Hwang, Da Hui Ha, Sang Min Lim, Chankyu Lee, Jinshi Zhao, et al. “Metabolic engineering of Escherichia coli to produce a monophosphoryl lipid A adjuvant.Metab Eng 57 (January 2020): 193–202. https://doi.org/10.1016/j.ymben.2019.11.009.
Ji Y, An J, Hwang D, Ha DH, Lim SM, Lee C, et al. Metabolic engineering of Escherichia coli to produce a monophosphoryl lipid A adjuvant. Metab Eng. 2020 Jan;57:193–202.
Ji, Yuhyun, et al. “Metabolic engineering of Escherichia coli to produce a monophosphoryl lipid A adjuvant.Metab Eng, vol. 57, Jan. 2020, pp. 193–202. Pubmed, doi:10.1016/j.ymben.2019.11.009.
Ji Y, An J, Hwang D, Ha DH, Lim SM, Lee C, Zhao J, Song HK, Yang EG, Zhou P, Chung HS. Metabolic engineering of Escherichia coli to produce a monophosphoryl lipid A adjuvant. Metab Eng. 2020 Jan;57:193–202.
Journal cover image

Published In

Metab Eng

DOI

EISSN

1096-7184

Publication Date

January 2020

Volume

57

Start / End Page

193 / 202

Location

Belgium

Related Subject Headings

  • Mice, Inbred BALB C
  • Mice
  • Metabolic Engineering
  • Lipid A
  • Immunoglobulin G
  • Escherichia coli
  • Biotechnology
  • Antibody Formation
  • Animals
  • Adjuvants, Immunologic