Increased Cordycepin Production in Using Combinatorial Metabolic Engineering Strategies.

As the first nucleoside antibiotic discovered in fungi, cordycepin, with its various biological activities, has wide applications. At present, cordycepin is mainly obtained from the natural fruiting bodies of . However, due to long production periods, low yields, and low extraction efficiency, harvesting cordycepin from natural is not ideal, making it difficult to meet market demands. In this study, an engineered YlCor-18 strain, constructed by combining metabolic engineering strategies, achieved efficient cordycepin production from glucose. First, the cordycepin biosynthetic pathway derived from was introduced into . Furthermore, metabolic engineering strategies including promoter, protein, adenosine triphosphate, and precursor engineering were combined to enhance the synthetic ability of engineered strains of cordycepin. Fermentation conditions were also optimized, after which, the production titer and yields of cordycepin in the engineered strain YlCor-18 under fed-batch fermentation were improved to 4362.54 mg/L and 213.85 mg/g, respectively, after 168 h. This study demonstrates the potential of as a cell factory for cordycepin synthesis, which will serve as the model for the green biomanufacturing of other nucleoside antibiotics using artificial cell factories.