Mining Actinomycetes' Metabolomes and Genomes for Anti‐ <i>Phytophthora infestans</i> Compounds

Actinomycetes are well-known for producing a diverse array of specialised metabolites with various bioactivities; yet, identifying metabolites with targeted activity against specific pathogens remains challenging. In this study, we employed a comparative metabolomic and genomic approach on 63 actinomycete strains differing in their ability to inhibit or alter the mycelial growth of Phytophthora infestans, the causal agent of potato late blight. This comparative approach efficiently pinpointed approximately 1000 mass spectrometry features linked to active extracts, out of 16,500 detected features. Our analysis putatively identified over 75 compounds with potential activity against P. infestans, including borrelidin, actinomycin D, antimycin A, macbecin I, myriocin and ikarugamycin. Our study shows that leveraging multi-omics analysis of phylogenetically related strains with differential activity is a promising strategy which, combined with a relatively high throughput metabolite extraction method, advanced mass spectrometry and cutting-edge tools for bacterial metabolite annotation and prediction, allowed a straightforward selection of interesting candidate compounds for the biological control of an important plant pathogen such as P. infestans. The methodology outlined here offers broader applicability for identifying bioactive compounds underlying any phenotype of interest, provided this phenotype varies in phylogenetically closely related strains.