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Metabolic engineering of Escherichia coli to produce a monophosphoryl lipid A adjuvant.
| Content Provider | Semantic Scholar |
|---|---|
| Author | An, Jinsu Hwang, Dohyeon Lim, Sang Min Lee, Chankyu Zhao, Jinshi Song, Hyun Kyu Yang, Eun Gyeong Zhou, Peng Chung, Hak Suk |
| Copyright Year | 2019 |
| 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. |
| File Format | PDF HTM / HTML |
| DOI | 10.1016/j.ymben.2019.11.009 |
| Alternate Webpage(s) | https://dukespace.lib.duke.edu/dspace/bitstream/handle/10161/19670/Hak_Suk_Chung_LpxE_MPLA_Metabolic_Engineering_2020.pdf?isAllowed=y&sequence=2 |
| PubMed reference number | 31786244 |
| Alternate Webpage(s) | https://doi.org/10.1016/j.ymben.2019.11.009 |
| Journal | Medline |
| Journal | Metabolic engineering |
| Language | English |
| Access Restriction | Open |
| Content Type | Text |
| Resource Type | Article |
