Synergistic Metabolism of Glucose and Formate Increases the Yield of Short-Chain Organic Acids in Escherichia coli,ACS Synthetic Biology

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Synergistic Metabolism of Glucose and Formate Increases the Yield of Short-Chain Organic Acids in Escherichia coli
ACS Synthetic Biology ( IF 3.7 ) Pub Date : 2022-01-03 , DOI: 10.1021/acssynbio.1c00289
Guipeng Hu _{1,

2,

3} , Liang Guo _{2,

3} , Cong Gao _{2,

3} , Wei Song _{1,

2,

3} , Liming Liu _{2,

3} , Xiulai Chen _{2,

3}

Affiliation

Microbial cell factories using a single carbon source (e.g., sugars) have been used to produce a wide variety of chemicals. However, this process is often accompanied by stoichiometric constraints on carbons and redox cofactors. Here, a synthetic pathway was designed and constructed in Escherichia coli to synergistically use glucose and formate as mixed carbon sources. By optimizing this synthetic pathway via enzyme mining, protein engineering, and bioprocess approaches, the yield of pyruvate from glucose was enhanced to 94% of the theoretical glycolysis yield, reaching 1.88 mol/mol. Finally, the optimized synthetic pathway was integrated with a phosphite reductase-based NADH regeneration system in malate-producing E. coli, resulting in the conversion of glucose into l-malate with a high yield of up to 1.65 mol/mol. This synergistic carbon metabolism strategy can be used to establish carbon- and energy-efficient productive processes.

中文翻译：

葡萄糖和甲酸的协同代谢提高大肠杆菌中短链有机酸的产量

使用单一碳源（例如糖）的微生物细胞工厂已被用于生产多种化学品。然而，这个过程通常伴随着对碳和氧化还原辅助因子的化学计量限制。在这里，在大肠杆菌中设计和构建了一条合成途径，以协同使用葡萄糖和甲酸盐作为混合碳源。通过酶挖掘、蛋白质工程和生物工艺方法优化这一合成途径，从葡萄糖中提取丙酮酸的产量提高到理论糖酵解产量的 94%，达到 1.88 mol/mol。最后，将优化的合成途径与产苹果酸大肠杆菌中基于亚磷酸还原酶的 NADH 再生系统相结合，从而将葡萄糖转化为l-苹果酸，产率高达 1.65 mol/mol。这种协同的碳代谢策略可用于建立碳和能源高效的生产过程。

更新日期：2022-01-21

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