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<p>D-Pantothenic acid (DPA), also known as vitamin B<sub>5</sub>, is a water-soluble organic acid, widely applied in foods, feeds, cosmetics, and medicines. Although numerous and rapidly developing cell factories have been established for DPA biosynthesis, there has been no report of any attempts to engineer <i>Yarrowia lipolytica</i> to synthesize DPA. To explore further possibilities in DPA biosynthesis, we tried to employ systematic metabolic engineering strategies to identify and break the potential bottlenecks in DPA biosynthesis by<i> Y. lipolytica</i>. By improving the rate-limiting steps of the DPA biosynthesis pathway, weakening the strongly competitive pathways, and enhancing the multiple cofactor supplies, a robust <i>Y. lipolytica</i> cell factory for DPA biosynthesis was successfully constructed. Consequently, the resulting strain DPA34 produced 2.18&#xa0;g/L DPA in a 5-L bioreactor, representing the first report of DPA production to date in <i>Y. lipolytica.</i> This work is believed to facilitate the development of <i>Y. lipolytica</i> for sustainable manufacturing of vitamin B<sub>5</sub> and its derivatives.</p> Graphical abstract <p></p>

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Metabolic engineering of Yarrowia lipolytica targeting bottlenecks to boost D-Pantothenic acid biosynthesis

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年1月27日

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  • Xing-Kai Li,
  • Nuo Zhang,
  • Hai-Peng Li,
  • Zheng-Yu Huang,
  • Gao-Yue Niu,
  • Chen-Yi Sun,
  • Jian-He Xu

摘要

D-Pantothenic acid (DPA), also known as vitamin B5, is a water-soluble organic acid, widely applied in foods, feeds, cosmetics, and medicines. Although numerous and rapidly developing cell factories have been established for DPA biosynthesis, there has been no report of any attempts to engineer Yarrowia lipolytica to synthesize DPA. To explore further possibilities in DPA biosynthesis, we tried to employ systematic metabolic engineering strategies to identify and break the potential bottlenecks in DPA biosynthesis by Y. lipolytica. By improving the rate-limiting steps of the DPA biosynthesis pathway, weakening the strongly competitive pathways, and enhancing the multiple cofactor supplies, a robust Y. lipolytica cell factory for DPA biosynthesis was successfully constructed. Consequently, the resulting strain DPA34 produced 2.18 g/L DPA in a 5-L bioreactor, representing the first report of DPA production to date in Y. lipolytica. This work is believed to facilitate the development of Y. lipolytica for sustainable manufacturing of vitamin B5 and its derivatives.

Graphical abstract