TY - JOUR
T1 - Metabolic engineering of Escherichia coli to produce a monophosphoryl lipid A adjuvant
AU - Ji, Yuhyun
AU - An, Jinsu
AU - Hwang, Dohyeon
AU - Ha, Da Hui
AU - Lim, Sang Min
AU - Lee, Chankyu
AU - Zhao, Jinshi
AU - Song, Hyun Kyu
AU - Yang, Eun Gyeong
AU - Zhou, Pei
AU - Chung, Hak Suk
PY - 2020/1/1
Y1 - 2020/1/1
N2 - 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.
AB - 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.
KW - Adjuvant
KW - Gram-negative bacterial outer membrane
KW - Lipid A 1-phosphatase
KW - Lipopolysaccharide biosynthesis
KW - Monophosphoryl lipid A
KW - Vaccine adjuvant
UR - http://www.scopus.com/inward/record.url?scp=85076692796&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85076692796&partnerID=8YFLogxK
U2 - 10.1016/j.ymben.2019.11.009
DO - 10.1016/j.ymben.2019.11.009
M3 - Article
C2 - 31786244
SN - 1096-7176
VL - 57
SP - 193
EP - 202
JO - Metabolic engineering
JF - Metabolic engineering
ER -