Scholarlink

<p>Microbial cell factories offer a sustainable route to plant-derived natural products, but yield drift and strain degeneration persist. Growth-coupled biosynthesis can continuously enrich high producers, yet specific product-responsive biosensors remain scarce and their population-level effects are unclear. Here, we describe a rapid transcriptome-mining workflow that, as proof-of-concept, delivers yeast biosensors for glycyrrhetinic acid and medicarpin. By fine-tuning <i>PDR5</i> promoter, we expand the dynamic range of the glycyrrhetinic acid sensor and wire it to an essential gene, establishing a growth-addiction circuit that increases titer by 46.8 % after subculture. Single-cell transcriptome reveals that the evolved strain population exhibits a completely different division of labor compared to the initial strain. Coupling does not eliminate phenotypic heterogeneity; instead, it amplifies a dedicated sub-population marked by discrete transcriptional signatures. Deletion of genes highly expressed in non-producing cells or enrichment of high-producing cell clusters can further boost population-level production. This study provides both a generalizable biosensor-discovery platform and single-cell-guided strategies for stabilizing and optimizing natural-product cell factories.</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

Design of the biosensor-dependent coupling system stabilizes the high-synthesis phenotype of cell factory

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年4月13日

查看全文
  • Lei Qin,
  • Bo Yang,
  • Rui Huang,
  • Haocheng Zhang,
  • Qiuyang Li,
  • Xinyi Li,
  • Yingqi Tan,
  • Wentao Sun,
  • Haiyang Jia,
  • Bing Hu,
  • Bo Lv,
  • Chun Li

摘要

Microbial cell factories offer a sustainable route to plant-derived natural products, but yield drift and strain degeneration persist. Growth-coupled biosynthesis can continuously enrich high producers, yet specific product-responsive biosensors remain scarce and their population-level effects are unclear. Here, we describe a rapid transcriptome-mining workflow that, as proof-of-concept, delivers yeast biosensors for glycyrrhetinic acid and medicarpin. By fine-tuning PDR5 promoter, we expand the dynamic range of the glycyrrhetinic acid sensor and wire it to an essential gene, establishing a growth-addiction circuit that increases titer by 46.8 % after subculture. Single-cell transcriptome reveals that the evolved strain population exhibits a completely different division of labor compared to the initial strain. Coupling does not eliminate phenotypic heterogeneity; instead, it amplifies a dedicated sub-population marked by discrete transcriptional signatures. Deletion of genes highly expressed in non-producing cells or enrichment of high-producing cell clusters can further boost population-level production. This study provides both a generalizable biosensor-discovery platform and single-cell-guided strategies for stabilizing and optimizing natural-product cell factories.