Re-discovery of MS-347a as a fungicide candidate through a new drug discovery platform with a multidrug-sensitive Saccharomyces cerevisiae screening system and the introduction of a global secondary metabolism regulator, laeA gene

  • Biosci Biotechnol Biochem. 2024 Jun 21;88(7):824-829. doi: 10.1093/bbb/zbae050.
Sota Honma  1  2 ,  Aoi Kimishima  1  2 ,  Atsushi Kimishima  3 ,  Masako Honsho  1  2 ,  Hiroki Kojima  1  2 ,  Toshiyuki Tokiwa  1  2 ,  Atsuka Nishitomi  1 ,  Satoshi Kato  1 ,  Naozumi Kondo  1 ,  Yasuko Araki  4 ,  Tadashi Takahashi  4 ,  Takumi Chinen  5 ,  Takeo Usui  6 ,  Shin-Ichi Fuji  7 ,  Kotaro Ito  4 ,  Yukihiro Asami  1  2
Affiliations
  • 1. Graduate School of Infection Control Sciences, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo, Japan.
  • 2. Ōmura Satoshi Memorial Institute, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo, Japan.
  • 3. Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamada-oka, Suita, Osaka, Japan.
  • 4. Research and Development Division, Kikkoman Corporation, 338 Noda, Noda-shii, Chiba, Japan.
  • 5. Department of Physiological Chemistry, Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, Japan.
  • 6. Graduate School of Life and Environmental Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, Japan.
  • 7. Faculty of Bioresource Sciences, Akita Prefectural University, 241-438 Kaidobata-Nishi, Nakano, Shimoshinjo, Akita, Japan.
PMID: 38664007 DOI: 10.1093/bbb/zbae050
Abstract

We found that the culture broth of fungi showed anti-fungal activity against multidrug-sensitive budding yeast. However, we could not identify the anti-fungal compound due to the small quantity. Therefore, we attempted to increase the productivity of the target compound by the introduction of a global secondary metabolism regulator, laeA to the strain, which led to the successful isolation of 10-folds greater amount of MS-347a (1) than Aspergillus sp. FKI-5362. Compound 1 was not effective against Candida albicans and the detailed anti-fungal activity of 1 remains unverified. After our anti-fungal activity screening, 1 was found to inhibit the growth of broad plant pathogenic Fungal species belonging to the Ascomycota. It is noteworthy that 1 showed little insecticidal activity against silkworms, suggesting its selective biological activity against plant pathogenic fungi. Our study implies that the combination strategy of multidrug-sensitive yeast and the introduction of laeA is useful for new anti-fungal drug discovery.

Keywords
Aspergillus sp; LaeA; fungicide candidates; multidrug-sensitive budding yeast; natural products.
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