Abstract
Cytidine is a precursor of several antiviral drugs. The pentose phosphate pathway (PPP) is primarily responsible for NADPH and 5-phospho-α-d-ribose 1-diphosphate as an important precursor of cytidine biosynthesis in Escherichia coli. To enhance cytidine production, we obtained the recombinant E. coli CYT15-gnd-prs-zwf that co-expressed the prs, zwf, and gnd genes encoding phosphoribosylpyrophosphate synthetase, glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase (three key enzymes in PPP) respectively. In fermentation experiments, strain CYT15-gnd-prs-zwf produced 735 mg cytidine/l using glucose as substrate, which was approx. 128 % higher than the cytidine production by the parental strain (CYT15). Co-expression of zwf, gnd, and prs decreased growth (3.2 %) slightly and increased glucose uptake (72 %). This is the first study to report increased cytidine production by increasing metabolic flux through the PPP in E. coli.
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Acknowledgments
We thank our colleagues for critical reading of the manuscript and providing valuable suggestions. This work was supported by the Research Program of Tianjin University of Science and Technology (No. 20100211) and by Program for Changjiang Scholars and Innovative Research Team in University (No. IRT1166).
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Fang, H., Xie, X., Xu, Q. et al. Enhancement of cytidine production by coexpression of gnd, zwf, and prs genes in recombinant Escherichia coli CYT15. Biotechnol Lett 35, 245–251 (2013). https://doi.org/10.1007/s10529-012-1068-3
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DOI: https://doi.org/10.1007/s10529-012-1068-3