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Background <p>Anthraquinones in the emodin family are produced by bacteria, fungi, and plants. They display various biological activities exploited, e.g., for crop protection, and may also be utilized as sustainable, bio-based colorants for the textile, paints, electronics, and cosmetic industries. Anthraquinone pigments from <i>Cortinarius</i> mushrooms have been used for artisan dyeing because they are stable, colorfast, and compatible with various dyeing methods. However, their chemical synthesis is complex and uneconomical, and harvesting wild mushrooms from forests in commercial quantities is not feasible.</p> Results <p>Here, we use genomics, transcriptomics, and synthetic biology to uncover the biosynthesis of the anthraquinone scaffold compounds emodin and endocrocin, and their methylation to the yellow pigments physcion and dermolutein in <i>Cortinarius semisanguineus</i> and <i>C.</i> sp. KIS-3. Both the nonreducing polyketide synthases (nrPKSs), and the regiospecific, fastidious <i>O-</i>methyltransferases (OMTs) are non-orthologous to their Ascomycete counterparts, suggesting a parallel evolutionary origin for the pathway in Basidiomycetes. The genes for the nrPKS and the OMTs are not all clustered in <i>Cortinarius</i>, revealing metabolic crosstalk among paralogous nrPKS biosynthetic gene clusters.</p> Conclusions <p>Heterologous biosynthesis of physcion and dermolutein in <i>Saccharomyces cerevisiae</i> opens the way to produce specific <i>Cortinarius</i> anthraquinones, and to modify these scaffolds to tune their chemistry towards their various applications.</p>

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Discovery of Cortinarius O-methyltransferases for the heterologous production of dermolutein and physcion

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年2月25日

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  • Pradhuman Jetha,
  • Dominik Mojzita,
  • Natalia Maiorova,
  • Jorg C. de Ruijter,
  • Hannu Maaheimo,
  • Satu Hilditch,
  • Gopal Peddinti,
  • Sandra Castillo,
  • Mervi Toivari,
  • Merja Penttilä,
  • István Molnár

摘要

Background

Anthraquinones in the emodin family are produced by bacteria, fungi, and plants. They display various biological activities exploited, e.g., for crop protection, and may also be utilized as sustainable, bio-based colorants for the textile, paints, electronics, and cosmetic industries. Anthraquinone pigments from Cortinarius mushrooms have been used for artisan dyeing because they are stable, colorfast, and compatible with various dyeing methods. However, their chemical synthesis is complex and uneconomical, and harvesting wild mushrooms from forests in commercial quantities is not feasible.

Results

Here, we use genomics, transcriptomics, and synthetic biology to uncover the biosynthesis of the anthraquinone scaffold compounds emodin and endocrocin, and their methylation to the yellow pigments physcion and dermolutein in Cortinarius semisanguineus and C. sp. KIS-3. Both the nonreducing polyketide synthases (nrPKSs), and the regiospecific, fastidious O-methyltransferases (OMTs) are non-orthologous to their Ascomycete counterparts, suggesting a parallel evolutionary origin for the pathway in Basidiomycetes. The genes for the nrPKS and the OMTs are not all clustered in Cortinarius, revealing metabolic crosstalk among paralogous nrPKS biosynthetic gene clusters.

Conclusions

Heterologous biosynthesis of physcion and dermolutein in Saccharomyces cerevisiae opens the way to produce specific Cortinarius anthraquinones, and to modify these scaffolds to tune their chemistry towards their various applications.