Developing Escherichia coli for the production of 3-hydroxy-3-methylbutyrate as a muscle-growth promoting agent

Sally J. Huang1, Martin J. Lai1 and Ethan I. Lan2*

1 Institute of Molecular Medicine and Bioengineering

2Department of Biological Science & Technology, National Yang Ming Chiao Tung University, Hsinchu, Taiwan

3-Hydroxy-3-methylbutyrate (HMB) is a valuable chemical compound that can serve as a nutritional supplement and pharmaceutical treatment for muscle loss diseases, including sarcopenia, as well as an enhancer of muscle mass and strength for athletes. Traditional chemical methods of HMB production involve the use of toxic substrates and catalysts, which can be hazardous. Although HMB can be derived from the microbial oxidation of β-methylbutyric acid by the fungus Galactomyces reessii, this approach is prohibitively expensive and challenging to operate. The use of this pathway allows for HMB production from different renewable resources such as sugars and glycerol. Hence, this study developed a synthetic metabolic pathway that enables the biosynthesis of HMB from acetyl-CoA, a central metabolite found in all organisms. The use of this pathway allows for HMB production from diverse renewable resources, such as sugars and glycerol. By introducing our synthetic HMB biosynthetic pathway, we successfully engineered a a benign strain of Escherichia coli to directly produce HMB from glucose, providing a safe and cost-effective route to HMB production.