Bioorganic & medicinal chemistry letters · 2024
The isolation of sclerotinin A as an anti-malarial compound by utilization of a global secondary metabolism regulator, laeA gene.
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Honma Sota, Kimishima Aoi, Kato Satoshi, Horiuchi Akari, Hokari Rei, Honsho Masako, Kojima Hiroki, Tokiwa Toshiyuki, Sugawara Akihiro, Iwatsuki Masato, Araki Yasuko, Takahashi Tadashi, Chinen Takumi, Usui Takeo, Ito Kotaro, Asami Yukihiro
Аннотация
Previously, we successfully introduced laeA gene into a fungal strain in order to significantly increase the production of a bioactive compound, allowing use to discover novel biological activity. To demonstrate the universal applicability of the laeA gene introduction strategy for taping the potential of fungal secondary metabolism, in this present study, we created a library of microorganisms which we had the laeA gene inserted, and from that library we aimed to isolate compounds which are produced at significantly greater quantities compared to the respective wild type strains. From this investigation, we were able to isolate sclerotinin A (1) from Pochonia sp. KTF-0504 strain. We revealed that 1 showed anti-malarial activity against Plasmodium falciparum parasite strains. On the other hands, 1 showed no anti-fungal activity against multidrug-sensitive budding yeast. Our study implies that the utilization of the laeA gene in fungi is a versatile method for the discovery of drug candidates.