Development of engineered Escherichia coli Nissle 1917 for biosynthesis of 3-Hydroxy-3-methylbutyrate to treat muscle loss disease

Tina W. Shih（施文婷）1, Ethan I. Lan2

Institute of Molecular Medicine and Bioengineering1, Department of Biological Science and Technology2

National Yang Ming Chiao Tung University, Hsinchu, Taiwan 

As the population in Taiwan continues to age, there is an increasing number of people suffering from sarcopenia, a disease that results in muscle loss. 3-Hydroxy-3-methylbutyrate (HMB) is a compound that can enhance protein production and prevent muscle breakdown. It is commonly used in clinical treatment to maintain muscle weight. Moreover, it is also a popular nutritional supplement for repairing muscle damage and increasing muscle weight and strength, making it in high demand for recreational use. Escherichia coli Nissle 1917 (EcN) is a probiotic strain of E. coli with anti-inflammatory and anti-infective properties, presenting it for treating diseases such as Crohn's disease and ulcerative colitis. Furthermore, the ample genetic tools availabe for E. coli make it an attractive candidate in engineered live therapeutics.

 Here, we aimed to develop an HMB-producing strain of EcN. By expressing the genes involved in the HMB biosynthetic pathway and modulating their expression, we showed successfully produce HMB using EcN. These results provide a potential live therapeutic that can be used for sustainable treatment of sarcopenia