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

Abstract

Microbial natural products have been a cornerstone of the pharmaceutical industry, but the supply of novel bioactive secondary metabolites has diminished due to extensive exploration of the most easily accessible sources, namely terrestrial Streptomyces species. The Persian Gulf is a unique habitat for marine sponges, which contain diverse communities of microorganisms including marine Actinobacteria. These exotic ecosystems may cradle rare actinomycetes with high potential to produce novel secondary metabolites. In this study, we harvested 12 different species of sponges from two locations in the Persian Gulf and isolated 45 symbiotic actinomycetes to assess their biodiversity and sponge-microbe relationships. The isolates were classified into Nocardiopsis (24 isolates), Streptomyces (17 isolates) and rare genera (4 isolates) by 16S rRNA sequencing. Antibiotic activity tests revealed that culture extracts from half of the isolates displayed growth inhibitory effects against seven pathogenic bacteria. Next, we identified five strains with the genetic potential to produce aromatic polyketides by genotyping ketosynthase genes responsible for synthesis of carbon scaffolds. The combined data led us to focus on Streptomonospora sp. PA3, since the genus has rarely been examined for its capacity to produce secondary metabolites. Analysis of culture extracts led to the discovery of a new bioactive aromatic polyketide denoted persiamycin A and 1-hydroxy-4-methoxy-2-naphthoic acid. The genome harbored seven gene clusters involved in secondary metabolism, including a tetracenomycin-type polyketide synthase pathway likely involved in persiamycin formation. The work demonstrates the use of multivariate data and underexplored ecological niches to guide the drug discovery process for antibiotics and anticancer agents.

Application of metabolomics on marine sponges and sponge-associated microorganisms: A review

“…This metabolomic application certainly greatly facilitates the determination of the species of marine sponge-associated microorganisms. Genomic characterization in several studies on marine sponge-associated microbes is very helpful in sorting out microorganisms that will produce active secondary metabolites based on the existing studies (Matroodi et al, 2020;Nouioui et al, 2017). Therefore, this PCR technique is chosen in metabolomic applications usually on species-specific characterization of organisms, especially for sponges and their associated microbes.…”

“…The HCA technique in the metabolomic application on sponges and their associated microbes is usually coupled with the PCR technique for the purpose of a genome sequence analysis in determining the genotype of an organism. The HCA technique in metabolomics coupled with the PCR technique will be described in a phylogenetic tree, where this phylogenetic tree visualizes the relationships between individuals or specific genotypes of a sponge or its associated microorganisms (Matroodi et al, 2020;Nouioui et al, 2017). Therefore, the HCA technique in the application of metabolomics on sponges and their associated microbes aims at individual clusters as well as species-specific determination.…”

The Methods of Digging for “Gold” within the Salt: Characterization of Halophilic Prokaryotes and Identification of Their Valuable Biological Products Using Sequencing and Genome Mining Tools

“…Genomes analysis of bacteria isolated from salt-pans with Plant Growth Promoting Features (microorganisms naturally capable of enhancing plant growth and protecting crops from pests) also determine antimicrobial agent encoding BGCs. Here, identified BGCs were similar to bacteriocin encoding BGCs [150] AntiSMASH was also utilized in the search for other BGCs, such as those responsible for the production of exopolysaccharide and pigment source [151], Persiamycin A [152], or carotenoids [153]. Due to its versatility, antiSMASH performs well in halophilic analysis, but it is usually combined with other rule-based or rule-independent tools for better predictions.…”

Recent methods for discovering novel bioactive metabolites, specifically antimicrobial agents, from marine-associated micro-organisms

“…Seven BGCs were identified, including a tetracenomycin‐type polyketide synthase pathway that was supposed to be involved in persiamycin synthesis (Matroodi et al . 2020).…”

“…pa3 has led to the discovery of a novel antimicrobial metabolite persiamycin A. Seven BGCs were identified, including a tetracenomycin-type polyketide synthase pathway that was supposed to be involved in persiamycin synthesis (Matroodi et al 2020).…”