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US 10,557,156 B2Granted
Bacterium constitutively producing monophosphoryl lipid A and method of producing monophosphoryl lipid A by using bacterium
AssigneeKorea Institute of Science and Technology
InventorsHak Suk Chung, Yu Hyun Ji, Jin Su An, Ick Chan Kwon, Eun Gyeong Yang
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Abstract
A bacterium that constitutively produces monophosphoryl lipid A (MLA) and a method of producing MLA by using the bacterium may simply produce MLA and a derivative thereof without acid hydrolysis, reduce a probability of natural mutation, and increase yields of MLA and a derivative thereof by constitutive expression of the MLA and derivative thereof.
Claims20
A recombinant bacterium that constitutively produces monophosphoryl lipid A (MLA) not conjugated to 2-keto-3-deoxy-D-manno-octulosonate (Kdo) moiety, wherein the recombinant bacterium comprises
- (a) (i) a genetic modification that increases the copy number of a gene encoding Lipid A 1-phosphatase (LpxE) polypeptide, (ii) at least one exogenous polynucleotide encoding a LpxE polypeptide, or (iii) a genetic modification wherein the endogenous promoter of an endogenous polynucleotide encoding a LpxE polypeptide is replaced with a heterologous promoter,
- (b) a chromosomal mutation that is a disruption in an endogenous polynucleotide that encodes an undecaprenyl pyrophosphate phosphatase (Und-PP phosphatase), and a chromosomal mutation that is a disruption in an endogenous polynucleotide that encodes a phosphatidylglycerophosphate phosphatase (PGP phosphatase), and
- (c) a mutation that is a disruption in an endogenous polynucleotide that encodes a 3-deoxy-D-manno-octulosonic acid transferase (KdtA) polypeptide.
Dependencies are inferred from the claim text.