# Fermentation conditions outweigh phylogeny in shaping the metabolome of novel Micromonospora strains: an integrated genomics-metabolomics analysis

## TL;DR

This study shows that how Micromonospora bacteria are grown has a bigger impact on their natural product production than their genetic relatedness.

## Contribution

The study reveals that cultivation conditions strongly influence metabolite profiles despite phylogenetic links to biosynthetic potential.

## Key findings

- Phylogenetic relationships correlate with biosynthetic potential but not with actual metabolite profiles.
- Cultivation conditions strongly modulate the expression of biosynthetic capabilities in Micromonospora.
- Novel Micromonospora species show significant potential for producing terpenes and polyketides.

## Abstract

The genus Micromonospora, a key member of the actinomycetes, has demonstrated considerable potential for natural product biosynthesis. In this study, we isolated 15 Micromonospora 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 Micromonospora 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 Micromonospora and highlights the value of investigating novel strains and applying diverse cultivation strategies in natural product discovery.

Our study provides a comprehensive genomic and metabolomic elucidation of the significant biosynthetic potential within the genus Micromonospora. 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.