Progress and Prospects of Natural Glycoside Sweetener Biosynthesis: A Review.

To achieve an adequate sense of sweetness with a healthy low-sugar diet, it is necessary to explore and produce sugar alternatives. Recently, glycoside sweeteners and their biosynthetic approaches have attracted the attention of researchers. In this review, we first outlined the synthetic pathways of glycoside sweeteners, including the key enzymes and rate-limiting steps. Next, we reviewed the progress in engineered microorganisms producing glycoside sweeteners, including de novo synthesis, whole-cell catalysis synthesis, and in vitro synthesis. The applications of metabolic engineering strategies, such as cofactor engineering and enzyme modification, in the optimization of glycoside sweetener biosynthesis were summarized. Finally, the prospects of combining enzyme engineering and machine learning strategies to enhance the production of glycoside sweeteners were discussed. This review provides a perspective on synthesizing glycoside sweeteners in microbial cells, theoretically guiding the bioproduction of glycoside sweeteners.