Bacteria of the genus Rhodococcus are well known for their ability to degrade a large range of organic compounds. Some rhodococci are free-living, saprophytic bacteria; others are animal and plant pathogens. Recently, several studies have shown that their genomes encode putative pathways for the synthesis of a large number of specialized metabolites that are likely to be involved in microbe-microbe and host-microbe interactions. To systematically explore the specialized metabolic potential of this genus, we here performed a comprehensive analysis of the biosynthetic coding capacity across publicly available rhododoccal genomes, and compared these with those of several Mycobacterium strains as well as that of their mutual close relative Amycolicicoccus subflavus. Comparative genomic analysis shows that most predicted biosynthetic gene cluster families in these strains are clade-specific and lack any homology with gene clusters encoding the production of known natural products. Interestingly, many of these clusters appear to encode the biosynthesis of lipopeptides, which may play key roles in the diverse environments were rhodococci thrive, by acting as biosurfactants, pathogenicity factors or antimicrobials. We also identified several gene cluster families that are universally shared among all three genera, which therefore may have a more ‘primary’ role in their physiology. Inactivation of these clusters by mutagenesis might help to generate weaker strains that can be used as live vaccines. The genus Rhodococcus thus provides an interesting target for natural product discovery, in view of its large and mostly uncharacterized biosynthetic repertoire, its relatively fast growth and the availability of effective genetic tools for its genomic modification.

Metabolomics, the global characterization of metabolite profiles, is becoming an increasingly powerful tool for research on secondary metabolite discovery and production. In this review we discuss examples of recent technological advances and biological applications of metabolomics in the search for chemical novelty and the engineered production of bioactive secondary metabolites.

Rhodococcus genome sequence analysis has revealed a surprisingly large (and unexplored) potential for the production of secondary metabolites. Also, putative γ-butyrolactone gene clusters have been identified in some Rhodococci. These signalling molecules are known to regulate secondary metabolism in Streptomyces. This work provides evidence for synthesis of a γ-butyrolactone(-like) molecule by Rhodococci (RJB), the first report in the Rhodococcus genus. The Rhodococcus jostii RHA1 RJB molecule was detected by a reporter system based on the γ-butyrolactone receptor protein (ScbR) of Streptomyces coelicolor. This RJB is structurally identical to 6-dehydro SCB2, the predicted precursor of the S. coelicolor γ-butyrolactone SCB2. The R. jostii RHA1 key RJB biosynthesis gene was identified (gblA): Deletion of gblA resulted in complete loss of RJB synthesis whereas higher RJB levels were detected when gblA was overexpressed. Interaction of the RJB molecule with ScbR indicates that communication may occur between these two Actinomycete genera in their natural habitat. Furthermore, RJB may provide a highly relevant tool for awakening cryptic secondary metabolic gene clusters in Rhodococci. This study provides preliminary evidence that R. jostii RHA1 indeed synthesizes diffusible molecules with antimicrobial activity, but a possible role for RJB in this remains to be established.

The search for novel bioactive compounds to overcome resistance to current therapeutics has become of utmost importance. Streptomyces spp. are one of the main sources of bioactive compounds currently used in medicine. In this work, five different global transcriptional regulators and five housekeeping genes, known to induce the activation or overproduction of secondary metabolites in Streptomyces coelicolor, were cloned in two separated constructs and expressed in 12 different strains of Streptomyces spp. from the in-house CS collection. These recombinant plasmids were also inserted into streptomycin and rifampicin resistant Streptomyces strains (mutations known to enhance secondary metabolism in Streptomyces). Different media with diverse carbon and nitrogen sources were selected to assess the strains’ metabolite production. Cultures were then extracted with different organic solvents and analysed to search for changes in their production profiles. An overproduction of metabolites already known to be produced by the biosynthesis wild-type strains was observed such as germicidin by CS113, collismycins by CS149 and CS014, or colibrimycins by CS147. Additionally, the activation of some compounds such as alteramides in CS090a pSETxkBMRRH and CS065a pSETxkDCABA or inhibition of the biosynthesis of chromomycins in CS065a in pSETxkDCABA when grown in SM10 was demonstrated. Therefore, these genetic constructs are a relatively simple tool to manipulate Streptomyces metabolism and explore their wide secondary metabolites production potential.

The rapid emergence of bacterial resistance to antibiotics has urged the need to find novel bioactive compounds against resistant microorganisms. For that purpose, different strategies are being followed, one of them being exploring secondary metabolite production in microorganisms from uncommon sources. In this work, we have analyzed the genome of 12 Streptomyces sp. strains of the CS collection isolated from the surface of leaf-cutting ants of the Attini tribe and compared them to four Streptomyces model species and Pseudonocardia sp. Ae150A_Ps1, which shares the ecological niche with those of the CS collection. We used a combination of phylogenetics, bioinformatics and dereplication analysis to study the biosynthetic potential of our strains. 51.5% of the biosynthetic gene clusters (BGCs) predicted by antiSMASH were unknown and over half of them were strain-specific, making this strain collection an interesting source of putative novel compounds.

This study evaluates the potential of various yeast strains as probiotic and postbiotic agents for agglutinating enteric pathogens, offering a preventive approach to gastrointestinal infections. Different yeast species were tested in vitro against a range of pathogenic bacteria, including enterotoxigenic Escherichia coli ETEC, Shigella flexneri, Salmonella enterica serovar Typhimurium, and Salmonella enterica serovar Enteritidis, to assess their capacity for pathogen agglutination. Additionally, inactivated yeasts were obtained using a novel chemical treatment and employed to explore their efficacy as postbiotic agents. The results suggest that both live and inactivated yeasts are able to agglutinate the different pathogens, potentially limiting bacterial colonization. Notably, we also demonstrated that Wickerhamomyces anomalus, Saccharomyces cerevisiae, and Pichia fermentans, exhibiting agglutination activity, were capable of reducing bacterial adhesion to HeLa cells in vitro. This research highlights yeast’s probiotic and postbiotic potential and supports the development of novel yeast-based products for preventing enteric infections.