Unveiling the specialized metabolism of Streptomyces lunaelactis spp.

The decline in the number of new antibiotics discoveries, related in parallel with an acceleration and generalization of the bacterial resistance phenomenon, the unfolding of the global health crisis, linked to the emergence of new viral pandemics, as well as the agro-industrial needs for new natural products less impacting the environment and human health, are examples of current driving elements that encourage research of new natural products. Over the past ten years or so, technological innovations allowing on one hand, the high-throughput and low-cost sequencing of bacterial genomes, and on the other, the high-resolution detection and identification of compounds, have offered an unmatched framework for discovery. During last decade, many innovative strategies have emerged, with the aim of providing access to biomolecules buried in nature. One of them is the bioprospecting of new microorganisms in ecological niches, described as extreme and so far unexplored, in order to maximize the chances of discovering new biomolecules. Streptomyces are soil bacteria, which actively participate in the recycling of organic biomass, and are also known to have an extremely developed secondary metabolism. Indeed, these Actinobacteria provide more than 50% of natural molecules of microbial origin used in human or animal medicine (antibacterial, antifungal, anti-tumor, etc) and in agro-industry (herbicides, insecticides, etc). The search for microorganisms native to karstic habitat called moonmilk, has led to the discovery of new strains of Streptomyces, including the recently described Streptomyces lunaelactis species.
The aim of this work is to characterize the specialized metabolome associated with the Streptomyces lunaelactis species, including identification of the molecules produced by this microorganism and determination of the genes responsible for their biosynthesis.
Through a comparative metabologenomic approach using 18 bacterial strains belonging to the S. lunaelactis species, this work has revealed their ability to produce bioactive molecules. Accordingly, the results of genome mining study of S. lunaelactis, combined with metabolomics studies, made it possible to evaluate the genetic predispositions of this species to produce specialized metabolites, as well as to experimentally validate some of these predictions. This work provides an overview on this species’ specialized metabolome and confirms that not only this microorganism, but also other Streptomyces derived from moonmilk, are abundant sources of new natural products. In addition, this work also exposes the risks associated with the dereplication of bacterial strain banks and investigates an innovative approach, which focuses on the evaluation of biosynthetic potential of strains within a single species, which shows a great promise in the search for new natural products.