Construction of a third NAD+ de novo biosynthesis pathway

Ding, Y.; Li, X.; Horsman, G. P.; Li, P.; Wang, M.; Li, J.; Zhang, Z.; Liu, W.; Wu, B.; Tao, Y.; Chen, Y.

doi:10.1101/2020.10.18.342451

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bioRxiv · 10.1101/2020.10.18.342451

Construction of a third NAD+ de novo biosynthesis pathway

Ding, Y.·Li, X.·Horsman, G. P.·Li, P.·Wang, M.·Li, J.·Zhang, Z.·Liu, W.·Wu, B.·Tao, Y.·Chen, Y.

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Abstract

Only two de novo biosynthetic routes to nicotinamide adenine dinucleotide (NAD+) have been described, both of which start from a proteinogenic amino acid and are tightly controlled. Here we establish a C3N pathway starting from chorismate in Escherichia coli as a third NAD+ de novo biosynthesis pathway. Significantly, the C3N pathway yielded extremely high cellular concentrations of NAD(H) in E. coli. Its utility in cofactor engineering was demonstrated by introducing the four-gene C3N module to cell factories to achieve higher production of 2,5-dimethylpyrazine and develop an efficient C3N-based whole-cell bioconversion system for preparing chiral amines. The wide distribution and abundance of chorismate in most kingdoms of life implies a general utility of the C3N pathway for modulating cellular levels of NAD(H) in versatile organisms.

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Ding, Y., Li, X., Horsman, G. P., Li, P., Wang, M., Li, J., Zhang, Z., Liu, W., Wu, B., Tao, Y., Chen, Y.. 2020-10-18. Construction of a third NAD+ de novo biosynthesis pathway. https://doi.org/10.1101/2020.10.18.342451

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