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<p><i>Cordyceps militaris</i> (<i>C. militaris</i>) is a prized medicinal fungus and a rich source of bioactive compounds, notably cordycepin. While the cordycepin biosynthetic gene cluster has been identified, the global regulatory networks orchestrating its production remain elusive. Here, we identify the Velvet protein CmVeA as a master regulator that synchronizes fungal development and cordycepin biosynthesis in <i>C. militaris.</i> Overexpression of <i>CmveA</i> significantly enhanced mycelial growth, sporulation, and cordycepin production by 2.3-fold, whereas knockout strains exhibited severe growth defects and a 60% reduction in yield. This enhancement was underpinned by the direct upregulation of the core biosynthetic genes <i>cns</i>1-4 at the transcriptional level. Furthermore, we confirmed that CmVeA physically interacts with CmVelB and CmLaeA to form the conserved Velvet complex. Our findings elucidate a sophisticated regulatory mechanism where CmVeA coordinates cellular development to secondary metabolism, positioning it as a prime engineering target for the construction of high-yield <i>C. militaris</i> cell factories.</p>

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The Velvet protein vea: a key positive regulator of growth and cordycepin biosynthesis in Cordyceps militaris

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年12月10日

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  • Wenbin Yu,
  • Xiaoyu Zhou,
  • Yufei Zhang,
  • Lihua Yao,
  • Yayi Tu,
  • Bin He

摘要

Cordyceps militaris (C. militaris) is a prized medicinal fungus and a rich source of bioactive compounds, notably cordycepin. While the cordycepin biosynthetic gene cluster has been identified, the global regulatory networks orchestrating its production remain elusive. Here, we identify the Velvet protein CmVeA as a master regulator that synchronizes fungal development and cordycepin biosynthesis in C. militaris. Overexpression of CmveA significantly enhanced mycelial growth, sporulation, and cordycepin production by 2.3-fold, whereas knockout strains exhibited severe growth defects and a 60% reduction in yield. This enhancement was underpinned by the direct upregulation of the core biosynthetic genes cns1-4 at the transcriptional level. Furthermore, we confirmed that CmVeA physically interacts with CmVelB and CmLaeA to form the conserved Velvet complex. Our findings elucidate a sophisticated regulatory mechanism where CmVeA coordinates cellular development to secondary metabolism, positioning it as a prime engineering target for the construction of high-yield C. militaris cell factories.