Highly Efficient Biosynthesis of Hypoxanthine in Escherichia coli and Transcriptome-Based Analysis of the Purine Metabolism

Nucleosides and purine analogues have multiple functions in cell physiology, food additives, and pharmaceuticals, and some are produced on a large scale using different microorganisms. However, biosynthesis of purines is still lacking. In the present study, we engineered the de novo purine biosynthesis pathway, branched pathways, and a global regulator to ensure highly efficient hypoxanthine production by Escherichia coli. The engineered strain Q2973 produced 1243 mg/L hypoxanthine in fed-batch fermentation, accompanied by an extremely low accumulation of byproducts such as acetate and xanthine. We also performed global gene expression analysis to illustrate the mechanism for improving hypoxanthine production. This study demonstrated the feasibility of large-scale hypoxanthine production byan engineered E. coli strain, and provides a reference for subsequent studies on purine analogues and nucleosides.