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<p>1,4-Butanediol (1,4-BDO) is a key commodity chemical used in the production of various products, including plastics, fibers, and polyesters. Here, a potent microbial platform for 1,4-BDO production from glucose via the L-glutamate-derived CoA-independent pathway was developed using <i>Corynebacterium glutamicum</i> as the host strain. Introducing a CoA-independent 1,4-BDO biosynthesis pathway and removing a metabolic flux bypass, the resulting initial strain produced 2.20&#xa0;g/L of 1,4-BDO from glucose. Upon prolonged cultivation, <i>C</i>. <i>glutamicum</i> showed an endogenous capacity to degrade 1,4-BDO. Transcriptomic analysis was conducted to identify genes potentially involved in this pathway. Among them, <i>fadH</i>, <i>aldH</i>, and <i>adhA</i> were verified as the key enzymes for 1,4-BDO degradation. The deletion of three dehydrogenase genes from the initial strain removed the product degradation and achieved an improved 1,4-BDO titer of 3.14&#xa0;g/L. Finally, fed-batch fermentation of the final strain was conducted, resulting in 13.4&#xa0;g/L of 1,4-BDO production. This work demonstrates the first successful development of <i>C</i>. <i>glutamicum</i> as a potent platform strain for the biosynthesis of 1,4-BDO.</p>

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Synthetic redesign of Corynebacterium glutamicum for 1,4-butanediol production via L-glutamate-derived CoA-independent pathway

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年11月26日

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  • Jinyoung Kim,
  • Hyeon Jin Kim,
  • Sukjae Han,
  • Moon Jeong Kim,
  • Gibyuck Byun,
  • Dae Geun Cha,
  • Seongmin Kim,
  • Kyung Jin Kim,
  • Jae Hun Lee,
  • Young Lyeol Yang,
  • Sang Woo Seo

摘要

1,4-Butanediol (1,4-BDO) is a key commodity chemical used in the production of various products, including plastics, fibers, and polyesters. Here, a potent microbial platform for 1,4-BDO production from glucose via the L-glutamate-derived CoA-independent pathway was developed using Corynebacterium glutamicum as the host strain. Introducing a CoA-independent 1,4-BDO biosynthesis pathway and removing a metabolic flux bypass, the resulting initial strain produced 2.20 g/L of 1,4-BDO from glucose. Upon prolonged cultivation, C. glutamicum showed an endogenous capacity to degrade 1,4-BDO. Transcriptomic analysis was conducted to identify genes potentially involved in this pathway. Among them, fadH, aldH, and adhA were verified as the key enzymes for 1,4-BDO degradation. The deletion of three dehydrogenase genes from the initial strain removed the product degradation and achieved an improved 1,4-BDO titer of 3.14 g/L. Finally, fed-batch fermentation of the final strain was conducted, resulting in 13.4 g/L of 1,4-BDO production. This work demonstrates the first successful development of C. glutamicum as a potent platform strain for the biosynthesis of 1,4-BDO.