Commercialization and Industrial Application of Trehalose CAS#99-20-7

Trehalose is a stable, non-reducing disaccharide composed of two glucose molecules linked by an α,α-1,1-glycosidic bond. It was first isolated from the ergot fungus of rye and later discovered to be widely distributed across the natural world — in plants, animals, and microorganisms, particularly fungi, algae, mosses, and invertebrates. Trehalose appears as white crystals; each molecule contains two molecules of crystalline water. It is soluble in water, glacial acetic acid, and hot ethanol, but insoluble in ether and acetone. When heated to 130 °C, it loses its crystalline water and becomes anhydrous.

Biological Function and Significance

Trehalose exhibits remarkable protective properties in living organisms. Under extreme environmental conditions—such as high temperature, freezing, dehydration, or high osmotic pressure—it forms a unique protective film on the surface of cells. This film helps stabilize proteins, cell membranes, and other biological structures, preventing denaturation and inactivation. Other natural sugars, such as sucrose or glucose, do not possess this capability. For this reason, trehalose is often referred to in the scientific community as the “sugar of life.”

Trehalose is abundant in various organisms, including lower ferns, algae, bacteria, fungi, yeasts, insects, and invertebrates. Among these, yeasts and molds contain particularly high levels—up to 20% of their dry weight. Due to its unique properties and broad biological presence, researchers have long focused on efficient extraction methods and large-scale industrial production of trehalose.

Current Preparation Methods

At present, several approaches have been developed for trehalose production, including chemical synthesis, microbial extraction, microbial fermentation, enzymatic synthesis, and genetic engineering.

1. Microbial Extraction Method

This method uses microorganisms such as yeasts, lactic acid bacteria, and molds that naturally contain trehalose. By modifying the growth conditions, trehalose accumulation within the cells is enhanced, after which it is extracted using appropriate techniques. However, this method has significant drawbacks — a long production cycle, low yield, and high cost — making large-scale industrial production difficult.

2. Microbial Fermentation Method

In this approach, trehalose is produced through microbial fermentation and subsequently extracted and purified from the fermentation broth. The key to this method lies in selecting high-yield strains through mutagenesis, cell fusion, or gene recombination. Japan’s Ajinomoto Co., Ltd. has successfully achieved industrial-scale production of trehalose using in vitro cultures of amino acid-producing bacteria. However, the conversion efficiency remains relatively low, and numerous by-products are generated during the process.

3. Enzymatic Synthesis

This method employs substrates such as glucose, maltose, or starch, which are converted into trehalose through enzymatic reactions. Despite its conceptual simplicity, the process faces challenges such as high energy consumption and the instability of phosphorylase enzymes, limiting its potential for industrial-scale implementation.

4. Genetic Engineering

Through genetic modification, trehalose synthase genes are introduced into microorganisms or plants, enabling the production of trehalose by engineered strains or transgenic species. This technique holds promise for efficient and sustainable trehalose production, although it remains primarily within the research and development stage.

5. Chemical Synthesis

Trehalose can also be synthesized chemically via an ethylene oxide addition reaction between 2,3,4,6-tetraacetylglucose and 3,4,6-triacetyl-1,2-dehydro-D-glucose. However, this method suffers from low yields and complex separation processes. As a result, chemical synthesis remains largely at the laboratory research level rather than in industrial application.

Conclusion

Trehalose, often called the “sugar of life,” is an exceptional disaccharide with powerful protective effects on biological systems. Although several production methods exist, challenges such as low yield, high cost, and limited scalability continue to restrict widespread industrial production. Ongoing advances in biotechnology, enzyme engineering, and genetic modification are expected to pave the way for more efficient and sustainable large-scale production of trehalose in the near future.