Osada Hiroyuki
Institute of Microbial Chemistry (BIKAKEN), Tokyo, Japan.
RIKEN Center for Sustainable Resource Science, Wako, Saitama, Japan.
Proc Jpn Acad Ser B Phys Biol Sci. 2025;101(1):8-31. doi: 10.2183/pjab.101.003.
This review outlines research on chemical biology using mainly microbial metabolites for agricultural applications. We established the RIKEN Natural Products Depository (NPDepo), housing many microbial metabolites, to support academic researchers who focus on drug discovery. We studied methods to stimulate secondary metabolism in microorganisms to collect various microbial products. The switch of secondary metabolism in microorganisms changes depending on the culture conditions. We discovered compounds that activate biosynthetic gene clusters in actinomycetes and filamentous fungi. Using these compounds, we succeeded in inducing the production of active compounds. Two approaches for screening bioactive compounds are described. One is phenotypic screening to explore antifungal compounds assisted by artificial intelligence (AI). AI can distinguish the morphological changes induced by antifungal compounds in filamentous fungi. The other is the chemical array method for detecting interactions between compounds and target proteins. Our chemical biology approach yielded many new compounds as fungicide candidates.
本综述概述了主要利用微生物代谢产物进行农业应用的化学生物学研究。我们建立了理化学研究所天然产物库（NPDepo），其中储存了许多微生物代谢产物，以支持专注于药物发现的学术研究人员。我们研究了刺激微生物次级代谢以收集各种微生物产物的方法。微生物次级代谢的转换会根据培养条件而变化。我们发现了能激活放线菌和丝状真菌中生物合成基因簇的化合物。利用这些化合物，我们成功诱导了活性化合物的产生。描述了两种筛选生物活性化合物的方法。一种是表型筛选，借助人工智能（AI）探索抗真菌化合物。AI可以区分丝状真菌中抗真菌化合物诱导的形态变化。另一种是检测化合物与靶蛋白之间相互作用的化学阵列法。我们的化学生物学方法产生了许多作为杀菌剂候选物的新化合物。
