The isolation of sclerotinin A as an anti-malarial compound by utilization of a global secondary metabolism regulator, laeA gene

被引:1
|
作者
Honma, Sota [1 ,2 ]
Kimishima, Aoi [1 ,2 ]
Kato, Satoshi [1 ]
Horiuchi, Akari [1 ]
Hokari, Rei [1 ,2 ]
Honsho, Masako [1 ,2 ]
Kojima, Hiroki [1 ,2 ]
Tokiwa, Toshiyuki [1 ,2 ]
Sugawara, Akihiro [1 ,2 ]
Iwatsuki, Masato [1 ,2 ]
Araki, Yasuko [3 ]
Takahashi, Tadashi [3 ]
Chinen, Takumi [4 ]
Usui, Takeo [5 ,6 ]
Ito, Kotaro [3 ]
Asami, Yukihiro [1 ,2 ]
机构
[1] Kitasato Univ, Grad Sch Infect Control Sci, 5-9-1 Shirokane,Minato Ku, Tokyo 1088641, Japan
[2] Kitasato Univ, Omura Satoshi Mem Inst, 5-9-1 Shirokane,Minato Ku, Tokyo 1088641, Japan
[3] Kikkoman Foods Inc, Res & Dev Div, 338 Noda, Noda, Chiba 2780037, Japan
[4] Univ Tokyo, Grad Sch Pharmaceut Sci, Dept Physiol Chem, 7-3-1 Hongo,Bunkyo Ku, Tokyo 1130033, Japan
[5] Univ Tsukuba, Inst Life & Environm Sci, 1-1-1 Tennodai, Ibaraki 3058572, Japan
[6] Univ Tsukuba, Microbiol Res Ctr Sustainabil MiCS, 1-1-1 Tennodai, Ibaraki 3058572, Japan
关键词
LaeA; Pochonia sp; Natural products; Anti-malarial candidates; MULTIDRUG-SENSITIVE YEAST; CONSTRUCTION; STRESS; DRUG; SEX;
D O I
10.1016/j.bmcl.2024.129947
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
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.
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页数:3
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