Scholarlink

<p>Prenylated phytochemicals like glabridin are valuable therapeutics and cosmetics, yet their plant scarcity and arduous synthesis hinder industrial supply. Rebuilding pathways in microbes is hampered by complex topology and carbon-cofactor competition. In this work, we design an artificial biosynthetic route using a “block-building” workflow, constructing independently optimizable upstream precursor-supply and downstream tailoring/prenylation blocks. Structure-informed retrosynthesis eliminates methylation to lock flux toward the isoflavone core, while a tunable yeast-embedded dimethylallyl pyrophosphate platform enables crucial prenylation. Screening alternative pterocarpan reductase sources resolves the rate-limiting pentacyclic ring-opening step, achieving glabridin synthesis. Hybridization serves as the block glue, enabling the diploid <i>Saccharomyces cerevisiae</i> strain to produce 0.24 mg/L of glabridin from glucose, with bioreactor validation reaching 1.20 mg/L. Extending this to a yeast × <i>Escherichia coli</i> consortium delivers 32.8 mg/L equol, confirming framework generality. In this work, the strategy converts intricate phytochemical pathways into plug-and-play genetic modules, enabling rapid fermentation-based manufacturing without extensive genome rewriting.</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

Block-building with yeast to elucidate an artificial pathway for de novo biosynthesis of glabridin

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年4月28日

查看全文
  • Hanning Deng,
  • Lu Cao,
  • Shan Li,
  • Changtai Zhang,
  • Weizhu Zeng,
  • Xinrui Zhao,
  • Jingwen Zhou

摘要

Prenylated phytochemicals like glabridin are valuable therapeutics and cosmetics, yet their plant scarcity and arduous synthesis hinder industrial supply. Rebuilding pathways in microbes is hampered by complex topology and carbon-cofactor competition. In this work, we design an artificial biosynthetic route using a “block-building” workflow, constructing independently optimizable upstream precursor-supply and downstream tailoring/prenylation blocks. Structure-informed retrosynthesis eliminates methylation to lock flux toward the isoflavone core, while a tunable yeast-embedded dimethylallyl pyrophosphate platform enables crucial prenylation. Screening alternative pterocarpan reductase sources resolves the rate-limiting pentacyclic ring-opening step, achieving glabridin synthesis. Hybridization serves as the block glue, enabling the diploid Saccharomyces cerevisiae strain to produce 0.24 mg/L of glabridin from glucose, with bioreactor validation reaching 1.20 mg/L. Extending this to a yeast × Escherichia coli consortium delivers 32.8 mg/L equol, confirming framework generality. In this work, the strategy converts intricate phytochemical pathways into plug-and-play genetic modules, enabling rapid fermentation-based manufacturing without extensive genome rewriting.