Designing a Minimal Artificial Glycolytic Pathway

yang, y.; Liu, Y.; zhang, j.; Yang, Q.; Cheng, J.; Chu, H.; Zhao, H.; Luo, M.; Lu, X.; Liu, D.; Sheng, X.; Zhang, Y.-H. P. J.; jiang, h.; Ma, Y.

doi:10.1101/2022.09.22.508994

bioRxiv · 10.1101/2022.09.22.508994

Designing a Minimal Artificial Glycolytic Pathway

yang, y.·Liu, Y.·zhang, j.·Yang, Q.·Cheng, J.·Chu, H.·Zhao, H.·Luo, M.·Lu, X.·Liu, D.·Sheng, X.·Zhang, Y.-H. P. J.·jiang, h.·Ma, Y.

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Abstract

The canonical glycolysis generates two molecules of acetyl-coenzyme A (acetyl-CoA) from one glucose through eleven cascade biochemical reactions. Here, we designed and constructed a Minimal Artificial Glycolytic (MAG) pathway consisting of only three types of biochemical reactions, with phosphoketolase as the core, combined with phosphatase and isomerase as auxiliary enzymes. It could theoretically achieve a 100% carbon yield to acetyl-CoA from any monosaccharide by integrating one-carbon condensation reaction. We tested the MAG pathway in vitro and in vivo, demonstrating the catabolism of typical C1-C6 carbohydrates to acetyl-CoA with yields from 82% to 95%. This novel glycolytic pathway provides a promising route for biomanufacturing with stoichiometric productivity from multiple carbon sources in the future.

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yang, y., Liu, Y., zhang, j., Yang, Q., Cheng, J., Chu, H., Zhao, H., Luo, M., Lu, X., Liu, D., Sheng, X., Zhang, Y.-H. P. J., jiang, h., Ma, Y.. 2022-09-22. Designing a Minimal Artificial Glycolytic Pathway. https://doi.org/10.1101/2022.09.22.508994

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