Glucose is the most abundant monosaccharide, serving as an essential energy source for cells in all domains of life and as an important feedstock for the biorefinery industry. The plant-biomass-sugar route dominates the current glucose supply, while the direct conversion of carbon dioxide into glucose through photosynthesis is not well studied. Here, we show that the potential of Synechococcus elongatus PCC 7942 for photosynthetic glucose production can be unlocked by preventing native glucokinase activity. Knocking out two glucokinase genes causes intracellular accumulation of glucose and promotes the formation of a spontaneous mutation in the genome, which eventually leads to glucose secretion. Without heterologous catalysis or transportation genes, glucokinase deficiency and spontaneous genomic mutation lead to a glucose secretion of 1.5 g/L, which is further increased to 5 g/L through metabolic and cultivation engineering. These findings underline the cyanobacterial metabolism plasticities and demonstrate their applications for supporting the direct photosynthetic production of glucose.

葡萄糖是最丰富的单糖，是生命各个领域细胞的重要能源，也是生物精炼工业的重要原料。植物-生物质-糖途径在目前的葡萄糖供应中占主导地位，而通过光合作用将二氧化碳直接转化为葡萄糖的研究尚未充分。在这里，我们表明，可以通过阻止天然葡萄糖激酶活性来释放细长聚球藻PCC 7942 光合葡萄糖生产的潜力。敲除两个葡萄糖激酶基因会导致细胞内葡萄糖积累，并促进基因组自发突变的形成，最终导致葡萄糖分泌。在没有异源催化或运输基因的情况下，葡萄糖激酶缺乏和自发基因组突变导致葡萄糖分泌量为1.5 g/L，通过代谢和培养工程进一步增加至5 g/L。这些发现强调了蓝藻代谢的可塑性，并证明了它们在支持直接光合作用生产葡萄糖方面的应用。