Streptomyces spp. From the Marine Sponge Antho dichotoma: Analyses of Secondary Metabolite Biosynthesis Gene Clusters and Some of Their Products

Abstract

Actinomycete bacteria from marine environments represent a potential source for new antibiotics and anti-tumor drugs. Ten strains belonging to the genus Streptomyces isolated from the marine sponge Antho dichotoma collected at the bottom of the Trondheim fjord (Norway) were screened for antibiotic activity. Since only few isolates proved to be bioactive in the conditions tested, we decided to gain an insight into their biosynthetic potential using genome sequencing and analysis. Draft genomes were analyzed for the presence of secondary metabolite biosynthesis gene clusters (BGCs) using antiSMASH software. BGCs specifying both known and potentially novel secondary metabolites were identified, suggesting that these isolates might be sources for new bioactive compounds. The results of this analysis also implied horizontal transfer of several gene clusters between the studied isolates, which was especially evident for the lantibiotic-and thiopeptide-encoding BGCs. The latter implies the significance of particular secondary metabolites for the adaptation of Streptomyces to the spatially enclosed marine environments such as marine sponges. Two bioactive isolates, one showing activity against both yeast and Bacillus subtilis, and one only against yeast were analyzed in details, leading to the identification of cycloheximide, linearmycins, and echinomycins that are presumably responsible for the observed bioactivities.

Bioactivity Screening and Gene-Trait Matching across Marine Sponge-Associated Bacteria

“…To establish a link between the secondary metabolite BGC repertoire and the growth inhibiting effect against pathogenic bacteria and cancer cell lines, laboratory-based screening methods combined with genome mining were performed followed by GTM analysis. The top five strains in terms of BGC frequency and abundance consisted of three Proteobacteria and two Actinobacteria strains, confirming their strong bioactivity potential observed before [ 44 , 72 , 73 , 74 ]. Nevertheless, the abundance and diversity of BGCs were not reflected in the phenotype of the strains as only one displayed antibacterial activity under the tested conditions.…”

High Potential for Secondary Metabolite Production of Paracoccus marcusii CP157, Isolated From the Crustacean Cancer pagurus

“…they found so far unrecognized potential for bioactivity in all tested strains, but distinct differences in the extent of antagonistic activity. Taking into account the different isolation sources of the here tested strains, “customized” bioactive compounds could be the result of adaptation to new environmental conditions ( Guerrero-Garzón et al, 2020 ). This is further supported considering the diverse metabolic profiles found in Paracoccus culture extracts ( Figure 6 ).…”

“…This high number of ECs is a proof for genetic flexibility and might provide the basis for fast adaptation to new environmental conditions ( Frank et al, 2015 ). The genetic components required for successful adaptation are often obtained via horizontal gene transfer from an existing bacterial community ( Guerrero-Garzón et al, 2020 ). The numerous ECs likely provide a competitive advantage for CP157, for instance due to additional BSGCs on plasmid pCP157_02.…”

Genotyping-Guided Discovery of Persiamycin A From Sponge-Associated Halophilic Streptomonospora sp. PA3

“…Moreover it has been shown that the non-methylated intermediate contributes to the survival of Listeria monocytogenes in the absence of menaquinones (Chen et al, 2017). Genome mining has been widely used in the identification of novel metabolites in terrestrial actinomycetes, in particular in Streptomyces (Belknap et al, 2020) and to a lesser extent in marine actinomycetes (Guerrero-Garzón et al, 2020;Lee et al, 2020). Recent examples include the discovery of neaumycin B (Kim et al, 2018) and new tunicamycins (Xu D. et al, 2018) from a marine-derived Micromonospora and Streptomyces sp.…”