Discovery of an antimalarial compound, burnettiene A, with a multidrug-sensitive <i>Saccharomyces cerevisiae</i> screening system based on mitochondrial function inhibitory activity-Reference-Cited by-同舟云学术

Discovery of an antimalarial compound, burnettiene A, with a multidrug-sensitive Saccharomyces cerevisiae screening system based on mitochondrial function inhibitory activity

Published:2024-07-09 Issue: Volume: Page:
ISSN:1347-6947
Container-title:Bioscience, Biotechnology, and Biochemistry
language:en
Short-container-title:

Author:

Kimishima Aoi¹²,Nishitomi Atsuka¹,Tsuruoka Iori¹,Sakai Katsuyuki¹,Hokari Rei¹²,Honsho Masako¹²,Honma Sota¹²,Ono Yuki¹,Kondo Naozumi¹,Tsutsumi Hayama¹²,Kikuchi Yuta¹,Tokiwa Toshiyuki²,Kojima Hiroki¹²,Higo Mayuka¹²,Nonaka Kenichi¹²,Inahashi Yuki¹²,Iwatsuki Masato¹²^ORCID,Fuji Shin-ichi³,Jang Jun-Pil⁴,Jang Jae-Hyuk⁴,Chinen Takumi⁵,Usui Takeo⁶^ORCID,Asami Yukihiro¹²^ORCID

Affiliation:

1. Graduate School of Infection Control Sciences, Kitasato University , Minato-ku, Tokyo , Japan

2. Ōmura Satoshi Memorial Institute, Kitasato University , Minato-ku, Tokyo , Japan

3. Faculty of Bioresource Sciences, Akita Prefectural University , Akita, Akita , Japan

4. Chemical Biology Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB) , Cheongju , South Korea

5. Department of Physiological Chemistry, Graduate School of Pharmaceutical Sciences, The University of Tokyo , 7-3-1 Hongo, Bunkyo, Tokyo , Japan

6. Institute of Life and Environmental Sciences, University of Tsukuba , Tsukuba, Ibaraki , Japan

Abstract

ABSTRACT In this paper, we describe our discovery of burnettiene A (1) as an antimalarial compound from the culture broth of Lecanicillium primulinum (current name: Flavocillium primulinum) FKI-6715 strain utilizing our original multidrug-sensitive yeast system. This polyene-decalin polyketide natural product was originally isolated as an antifungal active compound from Aspergillus burnettii. However, the antifungal activity of 1 has been revealed in only one fungal species, and the mechanism of action of 1 remains unknown. After the validation of mitochondrial function inhibitory of 1, we envisioned a new antimalarial drug discovery platform based on mitochondrial function inhibitory activity. We evaluated antimalarial activity and 1 showed antimalarial activity against Plasmodium falciparum FCR3 (chloroquine sensitive) and the K1 strain (chloroquine resistant). Our study revealed the utility of our original screening system based on a multidrug-sensitive yeast and mitochondrial function inhibitory activity for the discovery of new antimalarial drug candidates.

Funder

Japan Agency for Medical Research and Development

Korea Research Institute of Bioscience and Biotechnology

Ministry of Education of the Republic of Korea

Publisher

Oxford University Press (OUP)

Link

https://academic.oup.com/bbb/advance-article-pdf/doi/10.1093/bbb/zbae098/58809041/zbae098.pdf

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