Planomonospora: a Metabolomics Perspective on an Underexplored Actinobacteria Genus

Abstract

Despite an excellent track record, microbial drug discovery suffers from high rates of re-discovery. Better workflows for the rapid investigation of complex extracts are needed to increase throughput and allow early prioritization of samples. In addition, systematic characterization of poorly explored strains is seldomly performed. Here, we report a metabolomic study of 72 isolates belonging to the rare actinomycete genus Planomonospora, using a workflow of open access tools to investigate its secondary metabolites. The results reveal a correlation of chemical diversity and strain phylogeny, with classes of metabolites exclusive to certain phylogroups. We were able to identify previously reported Planomonospora metabolites, including the ureylene-containing oligopeptide antipain, the thiopeptide siomycin including new congeners and the ribosomally synthesized peptides sphaericin and lantibiotic 97518. In addition, we found that Planomonospora strains can produce the siderophore desferrioxamine or a salinichelin-like peptide. Analysis of the genomes of three newly sequenced strains led to the detection of 47 gene cluster families, of which several were connected to products found by LC-MS/MS profiling. This study demonstrates the value of metabolomic studies to investigate poorly explored taxa and provides a first picture of the biosynthetic capabilities of the genus Planomonospora.

Metabolomic investigation of the pseudouridimycin producer, a prolific streptomycete

“…1) whose HR-MS fragmentation pattern and UV spectrum (Supplementary Fig. 2) matched those of an authentic standard within this family, corresponding to the ureylene-containing oligopeptide antipain, 19 produced by non-ribosomal peptide synthetases in numerous bacteria and acting as a protease inhibitor. 20 Accordingly, we found the corresponding BGC in the ID38640 genome, showing 61-78% identical genes with the related BGCs in the MIBIG database 21 (Table 2).…”

Comparative Metabologenomics Analysis of Polar Actinomycetes

“…Targeted linking and automated approaches for accelerating drug discovery have been reviewed [ 39 , 53 ]. Recently, metabolomic and genomic data of 72 isolates belonging to the rare actinomycete genus Planomonospora were analysed using publicly available tools to link specialised metabolites to their corresponding BGCs [ 77 ]. The authors were able to manually pair siomycin congeners to a RiPP BGC and a new salinichelin-like metabolite to the known BGC encoding for erythrochelin.…”

A biaryl-linked tripeptide from Planomonospora leads to widespread class of minimal RiPP gene clusters

“…General conditions for strain cultivations were as described elsewhere. 4 For isolation and purification of compound 1A, 1.5 mL of a frozen stock of strain ID82291 was used to inoculate 15mL AF medium in a 50mL baffled flask. 18 After 72 hours,…”

“…3 In the search for new microbial secondary metabolites, we investigated 72 strains belonging to the rare actinomycete genus Planomonospora by extensive, HR-ESI-LC-MS/MS based metabolome mining of extracts. 4 Molecular networking analysis revealed a group of related features (see Figures S1-2), observed in samples from four phylogenetically related strains, with 16S rRNA gene sequences having 99.5 to 99.6% identity with Planomonospora algeriensis PM3. 4 In an HMBC experiment, a diagnostic cross-correlation was observed between both CH-5…”

“…4 Molecular networking analysis revealed a group of related features (see Figures S1-2), observed in samples from four phylogenetically related strains, with 16S rRNA gene sequences having 99.5 to 99.6% identity with Planomonospora algeriensis PM3. 4 In an HMBC experiment, a diagnostic cross-correlation was observed between both CH-5…”