Sustainable bioproduction of natural sugar substitutes: Strategies and challenges

Abstract

BackgroundWith the features of safety, stabilization, and low/no calorie, natural sugar substitutes have been widely used in food and beverage industries. Nevertheless, the low abundance of natural sugar substances makes the traditional plant extraction process neither economical nor environmentally friendly. Thus, the bioproduction of natural sugar substitutes by microbial cell factories has received great attention. Scope and approachNatural sugar substitutes can be classified into five types: monosaccharides, oligosaccharides, sugar alcohols, glycosides, and sweet-tasting proteins. This review aims to comprehensively summarize the recent advances in the bioproduction of the first four natural sugar substitutes, including synthetic pathways, production routes, and metabolic engineering strategies used to construct natural sugar substitute cell factories. The challenges and perspectives of the bioproduction of natural sugar substitutes are also discussed. Key findings and conclusionsThe bioproduction of natural sugar substitutes driven by synthetic biology has made great progress, and the microbial production of some natural sugar substitutes has been commercialized at an industrial scale. However, several challenges, such as the low activity of key enzymes, imbalance of metabolic modules caused by the overexpression of heterologous genes, and unknown exporters of some sugar substitutes, still exist. The emergence of new synthetic biology tools, including machine learning-based computational biodesign of cell factories, clustered regularly interspaced short palindromic repeats-based genome editing technology, and genetic circuit-based multimodular ordered control of cellular metabolism, brings promising opportunities to overcome the above challenges and make more natural sugar substitutes produced by microbial cell factories on the market.