Metabolic engineering of Escherichia coli to produce a monophosphoryl lipid A adjuvant
- Metabolic engineering of Escherichia coli to produce a monophosphoryl lipid A adjuvant
- 양은경; 정학숙; 임상민; 지유현; 황두현; 안진수; 하다희; 이찬규; Jinshi Zhao; 송현규; Pei Zhou
- 면역증강제; 모노포스포릴 지질 에이
- Issue Date
- Metabolic engineering
- VOL 57-202
- 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.
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