<p>Sorbic acid (SA) and its salts are among the world’s most widely used and safest food preservatives, yet their industrial production still relies on fossil fuel-derived feedstocks via chemical synthesis. Here, we report bioproduction of SA through microbial fermentation by decoding its biosynthetic pathway and metabolic engineering of <i>Saccharomyces cerevisiae</i> as a chassis. Here, we identify SA and its amide derivative sorbamide (SN) from <i>Myrothecium</i> sp. FJNU6, representing identification of SA from a microbial source. Genome sequencing and heterologous expression reveal the SA/SN biosynthetic gene cluster, comprising a highly reducing polyketide synthase (SoaA), a hydrolase (SoaB), and an amidotransferase (SoaC). To enable sustainable overproduction, we reconstitute and optimize the SoaA–SoaB pathway in <i>S. cerevisiae</i> through multilevel engineering, including dynamic promoter control, acetyl-CoA/malonyl-CoA pathway enhancement, peroxisomal compartmentalization, and two-stage fed-batch fermentation. These strategies collectively enable a production titer of 1.84 g/L SA in a 50 L bioreactor. This study uncovers a microbial biosynthetic pathway for SA/SN and establishes a microbial platform for SA production, providing a foundation for developing sustainable alternatives to fossil-based manufacturing.</p>

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Toward sustainable food preservatives: high-level production of sorbic acid in engineered Saccharomyces cerevisiae

  • Jianbin Xiao,
  • Wei Lin,
  • Xingtong Chen,
  • Haoyu Yu,
  • Chao Chen,
  • Qin Li,
  • Fan Cai,
  • Huaidong Zhang,
  • Huibin Chen,
  • Mingliang Zhang,
  • Yongjin J. Zhou,
  • Li Li

摘要

Sorbic acid (SA) and its salts are among the world’s most widely used and safest food preservatives, yet their industrial production still relies on fossil fuel-derived feedstocks via chemical synthesis. Here, we report bioproduction of SA through microbial fermentation by decoding its biosynthetic pathway and metabolic engineering of Saccharomyces cerevisiae as a chassis. Here, we identify SA and its amide derivative sorbamide (SN) from Myrothecium sp. FJNU6, representing identification of SA from a microbial source. Genome sequencing and heterologous expression reveal the SA/SN biosynthetic gene cluster, comprising a highly reducing polyketide synthase (SoaA), a hydrolase (SoaB), and an amidotransferase (SoaC). To enable sustainable overproduction, we reconstitute and optimize the SoaA–SoaB pathway in S. cerevisiae through multilevel engineering, including dynamic promoter control, acetyl-CoA/malonyl-CoA pathway enhancement, peroxisomal compartmentalization, and two-stage fed-batch fermentation. These strategies collectively enable a production titer of 1.84 g/L SA in a 50 L bioreactor. This study uncovers a microbial biosynthetic pathway for SA/SN and establishes a microbial platform for SA production, providing a foundation for developing sustainable alternatives to fossil-based manufacturing.