Natural sugar substitutes have the characteristics of safety, stability, low/no calories, etc., and have been widely used in food, beverage and other industries. According to the differences in molecular size and structure type, natural sugar substitutes can be divided into five types: monosaccharides, oligosaccharides, sugar alcohols, glycosides and sweet proteins.

At present, natural sugar substitutes are mainly derived from plant extraction, and sugars are secondary metabolites with low abundance in plants.

However, plant growth is season-dependent and the extraction process is complicated, which greatly limits the large-scale production of natural sugar substitutes.

Therefore, building a microbial cell factory that efficiently synthesizes natural sugar substitutes based on synthetic biology and metabolic engineering is of great significance for the large-scale production and application of natural sugar substitutes. Synthetic biology has many advantages in producing sugar substitutes.

First, produced by the method of synthetic biology, the reproduction speed of microorganisms is fast, which can get rid of the limitation of plant resources and produce such sweeteners in large quantities.

Secondly, most artificial sweeteners are still produced by traditional chemical methods, which have the characteristics of dangerous production environment, high energy consumption and heavy pollution.

If it is produced by the method of synthetic biology, it can be produced under normal temperature and pressure environment, and the raw material is only the nutrients required by microorganisms, which is safe and environmentally friendly, and meets the requirements of carbon neutrality.

Third, for sweeteners that are difficult to produce by chemical synthesis methods, synthetic biology methods may also be an effective alternative. The production of various sugar substitutes has involved biological fermentation and synthetic biology methods.

In fact, with the development of sugar substitute in recent years, the methods of biological fermentation and synthetic biology have been gradually integrated into the production of sugar substitute.

Erythritol is the first sugar alcohol commercially produced by a microbial fermentation method by using Candida lipolytica, which can accumulate high concentrations of erythritol, to ferment and produce erythritol.

Allulose is mainly produced by the method of biological enzyme catalysis, and the D-psicose-3-epimerase used can be produced by fermentation of Bacillus subtilis after genetic recombination.

In addition, Amyris has engineered yeast through synthetic biology to produce rebaudioside M, one of the steviol glycosides.

In the future, if the continuous optimization of strains and fermentation conditions can make the cost of products produced by synthetic biology methods compete with those produced by traditional methods, synthetic biology methods are expected to gradually become mainstream in the production of sugar substitutes.