Lacto-N-tetraose Biosynthesis from Lactose via Metabolically Rewired Escherichia Coli

Abstract

Researchers at the University of California, Davis have developed an engineered Escherichia coli platform for efficiently microbial production of lacto-N-tetraose (LNT), an important human milk oligosaccharide, directly from lactose as the sole carbon source. Through metabolic pathway rewiring, optimized lactose utilization, this technology enables a simple, scalable, and cost-effective fermentation process for industrial LNT production.

Full Description

This technology enables the production of lacto-N-tetraose (LNT), one of the major core human milk oligosaccharides, using a genetically engineered Escherichia coli strain that utilizes lactose as its sole carbon source. The invention combines precise tuning of β-galactosidase (LacZ) activity with engineered carbohydrate metabolism to efficiently channel carbon from lactose into UDP-sugar biosynthesis and LNT assembly. Compared with conventional chemical, enzymatic, or multi-substrate microbial production methods, this approach simplifies the manufacturing process while improving production efficiency and industrial scalability.

Applications

• Production of human milk oligosaccharides for use in infant formula and nutritional supplements. 
• Manufacture of LNT as a functional ingredient for foods and nutritional supplements. 
• Production of LNT for research, pharmaceutical development, and microbiome studies. 
• Platform for commercial microbial manufacturing of complex oligosaccharides. 
• Biotechnological platforms for sustainable rare sugar production.

Features/Benefits

• Simplifies feedstock inputs by using lactose as the sole carbon source and precursor. 
• Improves LNT yield and process efficiency by tuning LacZ expression to precisely control lactose hydrolysis. 
• Increases carbon flux toward UDP-sugar biosynthesis and LNT production through metabolic pathway engineering. 
• Enables stable, plasmid-free production through chromosomal integration of the biosynthetic pathway. 
• Reduces manufacturing costs and improves scalability compared with chemical, enzymatic, or multi-substrate production methods. 
• Provides a robust microbial fermentation platform suitable for industrial-scale LNT production.

Patent Status

Patent Pending