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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.

2022-09-22 synthetic biology
10.1101/2022.09.22.508994 bioRxiv
Show 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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