The discovery of pesticide lead compounds from microbial secondary metabolites

Microbial secondary metabolites have historically provided numerous agrochemicals with novel chemical scaffolds and distinctive modes of action, contributing substantially to modern pesticide science. However, the long-term accumulation of natural product screening efforts has resulted in the frequent rediscovery of known compounds, and this issue, combined with the global spread of pesticide-resistant pests and pathogens, has become a serious challenge in agrochemical research. This commemorative review summarizes the research achievements of the author focusing on the discovery of pesticide seed compounds from microbial secondary metabolites. Particular emphasis is placed on two original strategies developed by the author: the activation of silent biosynthetic gene clusters in filamentous fungi via introduction of the global transcriptional regulator laeA and the construction of innovative bioassay platforms for antifungal and insecticidal screening using drug-hypersensitive model organisms. These approaches successfully expanded accessible chemical diversity, markedly improved hit rates, and enabled the identification of bioactive compounds with novel molecular targets. Collectively, these studies demonstrate a practical and versatile framework for natural-product-based pesticide discovery that supports sustainable crop protection.