Recombinant Lactococcus lactis Expressing Human FGF21 Construction Services
One of the potential use of recombinant Lactococcus lactis strains is the treatment of metabolic disorders such as diabetes, obesity and auto-immune disorders such as atherosclerosis and encephalomyelitis. Creative Biolabs is one of the largest live biotherapeutics products (LBP) services suppliers. We have expertise and capabilities in providing high-quality LBP solutions.
Lactococcus Lactis: Heterologous Protein Delivery
Lactococcus lactis has made great progress from its initial discovery and application in dairy fermentation to the application of biotechnology in genetic engineering to produce various recombinant proteins and metabolites that transcend heterologous barriers. Key desirable characteristics of this Gram-positive lactic acid non-colonizing gut bacteria include its generally recognized safe (GRAS) status, probiotic properties, inclusion body and endotoxin free, surface display and exocrine techniques, and multiple selections of cloning and induced expression vectors. This has made Lactococcus lactis a desirable and promising host on par with other wel-established model bacterial or yeast systems such as Escherichia coli, Salmonella, Cerevisiae, and Bacillus subtilis.
Fig.1 Schematic representation of the NICE system development in Lactococcus lactis. (Mancha-Agresti, 2015)
Fibroblast Growth Factor 21 (FGF21)
FGF21 is predominantly expressed in the murine liver and thymus. FGF21 was found to be a mouse metabolic regulator with beneficial effects on glucose and lipid metabolism and insulin sensitivity in obese and diabetic mice. Transgenic mice overexpressing FGF21 in the liver showed resistance to diet-induced obesity and improved glycemic control. In diabetic rodents, FGF21 directly affects the endocrine function of the pancreas by enhancing insulin production and beta cell survival and reducing the maladaptive glucagon release.
Fig.2 Higher FGF21 levels in metabolically stressed individuals and clinical correlates. (Keuper, 2020)
Example: Recombinant Lactococcus lactis NZ3900 Expressing Human FGF21 Reduced Body Weight of Mice
FGF21 is a metabolic regulator that plays an important role in metabolic diseases such as obesity and diabetes. It is also expressed in mice, and the mouse source is highly homologous to human FGF21. In recent years, it has been widely studied as a potential drug target for the treatment of metabolic diseases. Scientists used Lactococcus lactis, a food-grade bacterium, as the host to express FGF21. In the NZ3900/PNZ8149 expression system, the LacF gene replaces the antibiotic resistance gene as the selective marker, which is safe and can reduce the antibiotic resistance crisis. The recombinant FGF21 expressing strain could express the human FGF21 well in the body and ameliorate obesity in Db/Db mice. Furthermore, a prolonged half-life of human FGF21 was achieved through oral gavage of the human FGF21 expressing strain. Therefore, oral human FGF21 may open up a new avenue for the treatment of obesity and related diseases.
Fig.3 Expression of recombinant Human FGF21 by Lactobacillus lactis NZ3900. (Cao, 2020)
As a common inducible host bacterium, Lactococcus lactis has an important role in research and application. Because of its potential in the production of heterologous proteins of therapeutic or technological value, Lactococcus lactis is becoming increasingly popular, among which the nisin-controlled gene expression (NICE) system is the most commonly used. In its combined form, Lactococcus lactis NZ3900/PNZ8149 is a crucial member of the NICE system. Creative Biolabs is a diverse, knowledgeable, and agile team, with a solid leadership universally recognized in the world of LBP. We have specialized in the custom services of LBP development for researchers around the world. If you are interested in our recombinant lactobacillus expression strains construction services, please contact us for more detail.
References
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Mancha-Agresti, P; et al. Future Clinical Applications of the Potential use of Lactic Acid Bacteria as Vehicles to Deliver DNA Vaccines. Austin J Vaccines & Immunother. 2015; 2(1): 1006.
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Keuper, M; et al. Circulating FGF21 levels in human health and metabolic disease. Experimental and Clinical Endocrinology & Diabetes. 2020, 128(11): 752-770.
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Cao, W.Y.; et al. Recombinant Lactococcus lactis NZ3900 expressing bioactive human FGF21 reduced body weight of Db/Db mice through the activity of brown adipose tissue. Benef Microbes. 2020, 11: 67-78.
For Research Use Only. Not intended for use in food manufacturing or medical procedures (diagnostics or therapeutics). Do Not Use in Humans.
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