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Studies of novel bioprobes isolated from rare natural sources using mutant yeasts

Abstract

For the discovery of novel drug candidates and bioprobes, it is important to investigate rare natural sources with unique screening methods. Our group tested 1000 original MeOH extracts from natural sources, such as plants and food ingredients using six types of mutant yeasts. In our experiments, Kuji amber was used as the rare domestic natural source and the growth-restoring activity (positive screening) of mutant yeast involving Ca2+-signal transduction was used as a unique screening method. A prominent new anti-allergy compound, named kujigamberol (15,20-dinor-5,7,9-labdatrien-18-ol) was isolated from Kuji amber and known compounds already isolated from modern plants were identified in Baltic and Dominican ambers. Kujigamberol and the methanol extract of Kuji amber (MEKA) exerted inhibitory activity against the degranulation of rat basophilic leukemia-2H3 (RBL-2H3) cells through the inhibition of Ca2+-influx and inhibited the production of leukotriene C4 (LTC4). The effects of kujigamberol and MEKA on rhinitis model were approximately five times more potent than those of the mometasone furoate. Thus, the combination of rare natural sources and unique mutant yeasts can yield valuable bioprobes as novel drug candidates and/or basic research reagents, to benefit humankind.

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Ken-ichi Kimura was awarded the Sumiki-Umezawa Memorial Award 2018 from the Japan Antibiotics Research Association. This review article is based on his award-winning research.

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Acknowledgements

The research presented herein was conducted in the Antibiotic Laboratory of RIKEN, Applied Microbiology Group of Snow Brand Milk Products. Co. Ltd, and the Chemical Biology Laboratory of Iwate University. On winning the Sumiki-Umezawa Memorial Award 2018 from the Japan Antibiotics Research Association, I thank all my students, collaborators, and colleagues. I especially express sincere thanks to Drs Kiyoshi Isono, Hiroyuki Osada (winner of the 1996 Sumiki-Umezawa Memorial Award), and Hiroyuki Koshino for guidance in chemical biology research and the structure elucidation (RIKEN), to Drs Tokichi Miyakawa and Eiko Tsuchiya for their collaboration of mutant yeasts (Hiroshima University) and Drs Nobuo Miyata and Makoto Yoshihama for the opportunity to research in the company (Snow Brand). We would like to thank Editage (www.editage.jp) and Emeritus Professor Don R Phillips, La Trobe University for English language editing. This work was supported by JSPS Kakenhi, JST, Sanriku Fund, NEDO, Iwate Prefecture, and Iwate University.

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The authors declare that they have no conflict of interest.

Correspondence to Ken-ichi Kimura.

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