<p>To discover novel natural compounds by awakening unexplored or silent BGCs in fungi, our research group has explored the cultured broths of the <i>laeA</i>-introduced mutant fungal strains. In this study, we report the isolation of a new benzoyl sesquiterpenoid, aoganolide (<b>4</b>), as well as three known compounds, decarboxyaltenusin (<b>1</b>), altenusin (<b>2</b>), and penipyranicin B (<b>3</b>), from the cultured broth of <i>Talaromyces</i> sp. KTF-0021, which was a <i>laeA</i>-introduced mutant of FKI-5759 strain. The planar structure of <b>4</b> was elucidated by spectroscopic analysis and the absolute configuration of <b>4</b> was determined by the calculated ECD spectral method. Among them, <b>4</b> showed antimalarial activity with IC<sub>50</sub> values of 4.37 and 6.46 µg ml<sup>−1</sup> against <i>Plasmodium falciparum</i> FCR3 and K1 strains, respectively. The <i>laeA</i>-introduced mutant strain produced <b>2</b>, <b>3</b>, and <b>4</b> with higher productivity (47,&#xa0;623, and 38 mg l<sup>−1</sup>) than the wild-type strain (1.4, 0.8, and 7.7 mg l<sup>−1</sup>), respectively, suggesting this method is useful to expand the chemical diversity of natural products.</p>

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New benzoyl sesquiterpenoid, aoganolide, produced by Talaromyces sp. KTF-0021 strain (laeA-introduced mutant of FKI-5759 strain)

  • Karin Hamada,
  • Yoshihiro Watanabe,
  • Yuta Kikuchi,
  • Hayama Tsutsumi,
  • Haruki Azami,
  • Hiroki Kojima,
  • Sho Kato,
  • Akihiro Sugawara,
  • Yuki Inahashi,
  • Kenichi Nonaka,
  • Rei Hokari,
  • Aki Ishiyama,
  • Yasuko Araki,
  • Kona Yamashita,
  • Tadashi Takahashi,
  • Kotaro Ito,
  • Yukihiro Asami,
  • Masato Iwatsuki

摘要

To discover novel natural compounds by awakening unexplored or silent BGCs in fungi, our research group has explored the cultured broths of the laeA-introduced mutant fungal strains. In this study, we report the isolation of a new benzoyl sesquiterpenoid, aoganolide (4), as well as three known compounds, decarboxyaltenusin (1), altenusin (2), and penipyranicin B (3), from the cultured broth of Talaromyces sp. KTF-0021, which was a laeA-introduced mutant of FKI-5759 strain. The planar structure of 4 was elucidated by spectroscopic analysis and the absolute configuration of 4 was determined by the calculated ECD spectral method. Among them, 4 showed antimalarial activity with IC50 values of 4.37 and 6.46 µg ml−1 against Plasmodium falciparum FCR3 and K1 strains, respectively. The laeA-introduced mutant strain produced 2, 3, and 4 with higher productivity (47, 623, and 38 mg l−1) than the wild-type strain (1.4, 0.8, and 7.7 mg l−1), respectively, suggesting this method is useful to expand the chemical diversity of natural products.