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

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Ji, Y; An, J; Hwang, D; Ha, DH; Lim, SM; Lee, C; Zhao, J; Song, HK; Yang, EG; Zhou, P; Chung, HS

Published Date

  • January 2020

Published In

Volume / Issue

  • 57 /

Start / End Page

  • 193 - 202

PubMed ID

  • 31786244

Pubmed Central ID

  • PMC6960009

Electronic International Standard Serial Number (EISSN)

  • 1096-7184

Digital Object Identifier (DOI)

  • 10.1016/j.ymben.2019.11.009

Language

  • eng

Conference Location

  • Belgium