Scholarlink

<p>L-(+)-tartaric acid (L-TA) is a high-value chiral organic acid essential for food and pharmaceuticals. Despite its industrial importance, sustainable green production is constrained by the lack of a fully defined biosynthetic pathway. Here, we report the de novo biosynthesis of L-TA in <i>Saccharomyces cerevisiae</i> through reaction-guided enzyme mining, experimental validation, and Enzyme Commission-specific Catalytic Hybrid Optimizer (ECHO)-assisted enzyme prioritization. We first elucidate the elusive two-step conversion from precursor 5-keto-D-gluconic acid (5-KGA) to L-TA, catalyzed by transketolase (TK) and succinate semialdehyde dehydrogenase (SSDH). To optimize this critical step, we develop the ECHO. This multimodal framework integrates sequence, substrate, and pocket-aware structural information to identify high-performance TK-SSDH pairs. By integrating this pathway with de novo precursor synthesis, cofactor engineering, and semi-rational protein engineering, a final L-TA titer of 6.59 mg L<sup>−1</sup> was achieved in a 5-L bioreactor. By connecting computational mining and metabolic assembly through a multi-module engineering strategy, our study establishes a green platform for L-TA production and demonstrates an effective workflow for synthetic pathway design.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

De novo L-(+)-tartaric acid biosynthesis in multi-modular engineered yeasts

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年8月1日

查看全文
  • Xuan Zhou,
  • Jiaheng Hou,
  • Zikai Wang,
  • Zhendong Li,
  • Yang Li,
  • Xitong Li,
  • Xianhao Xu,
  • Yanfeng Liu,
  • Jianghua Li,
  • Guocheng Du,
  • Dacheng Ma,
  • Jian Tang,
  • Jian Chen,
  • Xueqin Lv,
  • Long Liu

摘要

L-(+)-tartaric acid (L-TA) is a high-value chiral organic acid essential for food and pharmaceuticals. Despite its industrial importance, sustainable green production is constrained by the lack of a fully defined biosynthetic pathway. Here, we report the de novo biosynthesis of L-TA in Saccharomyces cerevisiae through reaction-guided enzyme mining, experimental validation, and Enzyme Commission-specific Catalytic Hybrid Optimizer (ECHO)-assisted enzyme prioritization. We first elucidate the elusive two-step conversion from precursor 5-keto-D-gluconic acid (5-KGA) to L-TA, catalyzed by transketolase (TK) and succinate semialdehyde dehydrogenase (SSDH). To optimize this critical step, we develop the ECHO. This multimodal framework integrates sequence, substrate, and pocket-aware structural information to identify high-performance TK-SSDH pairs. By integrating this pathway with de novo precursor synthesis, cofactor engineering, and semi-rational protein engineering, a final L-TA titer of 6.59 mg L−1 was achieved in a 5-L bioreactor. By connecting computational mining and metabolic assembly through a multi-module engineering strategy, our study establishes a green platform for L-TA production and demonstrates an effective workflow for synthetic pathway design.