Designing a Minimal Artificial Glycolytic Pathway

Author:

Yang Yiqun,Liu Yuwan,Zhang Jie,Yang Qiaoyu,Cheng Jian,Chu Huanyu,Zhao Haodong,Luo Mengting,Lu Xiaoyun,Liu Dingyu,Sheng Xiang,Zhang Yi-Heng P. J.,Jiang Huifeng,Ma Yanhe

Abstract

AbstractThe 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.

Publisher

Cold Spring Harbor Laboratory

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