Fermentation conditions outweigh phylogeny in shaping the metabolome of novel <i>Micromonospora</i> strains: an integrated genomics-metabolomics analysis

The genus <i>Micromonospora</i>, a key member of the actinomycetes, has demonstrated considerable potential for natural product biosynthesis. In this study, we isolated 15 <i>Micromonospora</i> spp. strains from desert soil and marine sediment samples, eight of which represent four novel species. To explore the biosynthetic capacity of this genus, we performed an integrated analysis of <i>Micromonospora</i> reference genomes. Pan-genomic analysis further unveiled the core biosynthetic characteristics of the genus responsible for producing terpenes and polyketides. Further multi-omics investigation, combining genomic and metabolomic data, uncovered a positive correlation between phylogenetic relationships and biosynthetic potential, alongside a decoupling of metabolic profiles. Notably, metabolomic findings emphasized the dominant influence of culture conditions on the expression of biosynthetic capabilities. Overall, our study provides a comprehensive elucidation of the biosynthetic potential of the genus <i>Micromonospora</i> and highlights the value of investigating novel strains and applying diverse cultivation strategies in natural product discovery.IMPORTANCEOur study provides a comprehensive genomic and metabolomic elucidation of the significant biosynthetic potential within the genus <i>Micromonospora</i>. It reveals a core biosynthetic capacity for terpenes and polyketides that is phylogenetically linked, whereas the resulting natural product repertoire is subject to strong modulation by cultivation conditions. These findings underscore the critical importance of exploring novel species and employing diverse cultivation strategies to unlock the full potential of microbial resources for natural product discovery.