Efficient production of glycine from glucose via a two-stage biosynthetic strategy

Background High-quality glycine is widely used in the cosmetics and pharmaceutical industries. Conventional chemical synthesis of glycine is disfavored because it relies on toxic reagents and complex downstream purification. Results Herein, we established an efficient two-step biosynthetic process for producing glycine from glucose. First, an l -threonine−overproducing strain was used to synthesis l -threonine via 50 L fed-batch fermentation, achieving a titer of 119.3 g/L. Then, a highly active l -threonine aldolase ( Pp LTA) was screened to convert l -threonine into glycine. To overcome thermodynamic and acetaldehyde inhibition constraints, an acetaldehyde elimination system was constructed via introducing Sc ADH1 and Sc CR, which increased the molar conversion yield of glycine increased by 3.9-fold. Whole-cell catalysis gave a significantly higher conversion yield than crude enzyme preparations. A whole-cell co-expressing Pp LTA, Sc ADH1, and Sc CR was subsequently constructed. Finally, at 50 L scale, direct conversion of l -threonine fermentation broth afforded a glycine titer of 65.4 g/L within 24 h, with a molar conversion yield of 87.2%, In addition, 99.8% pure glycine was obtained with a yield of 76.6% via separation. Conclusions An efficient two-step process for converting glucose to glycine was developed and successfully validated. Evaluation at the 50 L scale demonstrated record-high glycine production performance. This work provides a promising technological route for the industrial manufacture of high-quality glycine. Graphical