Genome Mining of the Marine Actinomycete Streptomyces sp. DUT11 and Discovery of Tunicamycins as Anti-complement Agents

Xu, Xiaofei; Chen, Liang‐Yu; Chen, Chao; Tang, Ya‐Jie; Bai, Fengwu; Su, Chun; Zhao, Xin‐Qing

doi:10.3389/fmicb.2018.01318

Cited by 21 publications

(16 citation statements)

References 74 publications

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“…Marine ecosystems are attracting particular attention, where extreme and rapidly changing environmental conditions such as differences in pressure, salinity, pH, light intensity, temperature and oligotrophic conditions are believed to be linked to secondary metabolites production (Abdelmohsen et al, 2014; van der Meij et al, 2017). In this respect, marine ecosystems have been a particularly fruitful source of Streptomyces strains which have the potential to produce new bioactive NPs (Hassan et al, 2017; Jin et al, 2018; Xu et al, 2018), with marine Streptomyces being isolated from seashores, coastal waters, bottom sediments, fishes, molluscs, sponges, seaweeds and mangroves (Manivasagan et al, 2014; Ser et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

Comparative Genomics of Marine Sponge-Derived Streptomyces spp. Isolates SM17 and SM18 With Their Closest Terrestrial Relatives Provides Novel Insights Into Environmental Niche Adaptations and Secondary Metabolite Biosynthesis Potential

et al. 2019

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The emergence of antibiotic resistant microorganisms has led to an increased need for the discovery and development of novel antimicrobial compounds. Frequent rediscovery of the same natural products (NPs) continues to decrease the likelihood of the discovery of new compounds from soil bacteria. Thus, efforts have shifted toward investigating microorganisms and their secondary metabolite biosynthesis potential, from diverse niche environments, such as those isolated from marine sponges. Here we investigated at the genomic level two Streptomyces spp. strains, namely SM17 and SM18, isolated from the marine sponge Haliclona simulans , with previously reported antimicrobial activity against clinically relevant pathogens; using single molecule real-time (SMRT) sequencing. We performed a series of comparative genomic analyses on SM17 and SM18 with their closest terrestrial relatives, namely S. albus J1074 and S. pratensis ATCC 33331 respectively; in an effort to provide further insights into potential environmental niche adaptations (ENAs) of marine sponge-associated Streptomyces , and on how these adaptations might be linked to their secondary metabolite biosynthesis potential. Prediction of secondary metabolite biosynthetic gene clusters (smBGCs) indicated that, even though the marine isolates are closely related to their terrestrial counterparts at a genomic level; they potentially produce different compounds. SM17 and SM18 displayed a better ability to grow in high salinity medium when compared to their terrestrial counterparts, and further analysis of their genomes indicated that they possess a pool of 29 potential ENA genes that are absent in S. albus J1074 and S. pratensis ATCC 33331. This ENA gene pool included functional categories of genes that are likely to be related to niche adaptations and which could be grouped based on potential biological functions such as osmotic stress, defense; transcriptional regulation; symbiotic interactions; antimicrobial compound production and resistance; ABC transporters; together with horizontal gene transfer and defense-related features.

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Section: Introductionmentioning

confidence: 99%

Comparative Genomics of Marine Sponge-Derived Streptomyces spp. Isolates SM17 and SM18 With Their Closest Terrestrial Relatives Provides Novel Insights Into Environmental Niche Adaptations and Secondary Metabolite Biosynthesis Potential

et al. 2019

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“…The natural source-derived anti-complement drugs are mainly from plants (Xu, Chen & Zhao, 2015). So far, the known BGCs for microbial-derived anti-complement agents include the complestatin BGC (Chiu et al, 2001) and tunicamycin BGC (Xu et al, 2018). The complestatin BGC is an NRPS BGC and the tunicamycin BGC is a nucleoside BGC.…”

Section: Discussionmentioning

confidence: 99%

“…S063 were extracted using 20 mL MeOH or 20 mL EtOAc, and then the resultant extracts were dried and re-dissolved into 1 mL MeOH or 1 mL water for use. The protocol to evaluate the ACA was based on the modified method from our laboratory (Xu et al, 2018). The absorbance at 405 nm of the supernatants (200 µL) was measured with a spectrophotometer (Multiskan GO 1510; Thermo Fisher Scientific, Vantaa, Finland).…”

Section: Methodsmentioning

confidence: 99%

“…Among various bioactivities of secondary metabolites from actinobacteria, anti-complement compounds are of great interest for drug discovery to treat numerous diseases resulting from inappropriate or excessive activation of the human complement system (Morgan & Harris, 2015). Until now, such compounds isolated from algae and plants have been studied (Wen et al, 2017; Jin et al, 2015), whereas compounds with such activities have been limitedly explored in microorganisms (Xu et al, 2018). So far, only two compound families from microorganisms have been reported to have anti-complement activity (ACA); one is complestatin and its analogs (Kaneko, Kamoshida & Takahashi, 1989), and the other is tunicamycin, which was reported in our recent work (Kaneko, Kamoshida & Takahashi, 1989).…”

Section: Introductionmentioning

confidence: 99%

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Analysis of the complete genome sequence of a marine-derived strainStreptomycessp. S063 CGMCC 14582 reveals its biosynthetic potential to produce novel anti-complement agents and peptides

Chen

Cui

et al. 2019

PeerJ

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Genome sequences of marine streptomycetes are valuable for the discovery of useful enzymes and bioactive compounds by genome mining. However, publicly available complete genome sequences of marine streptomycetes are still limited. Here, we present the complete genome sequence of a marine streptomycete Streptomyces sp. S063 CGMCC 14582. Species delineation based on the pairwise digital DNA-DNA hybridization and genome comparison ANI (average nucleotide identity) value showed that Streptomyces sp. S063 CGMCC 14582 possesses a unique genome that is clearly different from all of the other available genomes. Bioactivity tests showed that Streptomyces sp. S063 CGMCC 14582 produces metabolites with anti-complement activities, which are useful for treatment of numerous diseases that arise from inappropriate activation of the human complement system. Analysis of the genome reveals no biosynthetic gene cluster (BGC) which shows even low similarity to that of the known anti-complement agents was detected in the genome, indicating that Streptomyces sp. S063 CGMCC 14582 may produce novel anti-complement agents of microbial origin. Four BGCs which are potentially involved in biosynthesis of non-ribosomal peptides were disrupted, but no decrease of anti-complement activities was observed, suggesting that these four BGCs are not involved in biosynthesis of the anti-complement agents. In addition, LC-MS/MS analysis and subsequent alignment through the Global Natural Products Social Molecular Networking (GNPS) platform led to the detection of novel peptides produced by the strain. Streptomyces sp. S063 CGMCC 14582 grows rapidly and is salt tolerant, which benefits efficient secondary metabolite production via seawater-based fermentation. Our results indicate that Streptomyces sp. S063 has great potential to produce novel bioactive compounds, and also is a good host for heterologous production of useful secondary metabolites for drug discovery.

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“…In fact, the number of new chemical structures reported from marine organisms has continuously increased with over 200 novel metabolites described every year (Raimundo et al, 2018). Marine sponge species (phylum Porifera) host diverse microbial populations in their mesohyl matrix that include bacteria, fungi and archaea, as well as viruses (Xu X. N. et al, 2018;Achlatis et al, 2019), which may constitute 35-60% of the sponge volume. Marine sponges harbor at least 32 bacterial phyla including Acidobacteria, Actinobacteria, Cyanobacteria and Proteobacteria (Abdelmohsen et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2020

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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.

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Genome Mining of the Marine Actinomycete Streptomyces sp. DUT11 and Discovery of Tunicamycins as Anti-complement Agents

Cited by 21 publications

References 74 publications

Comparative Genomics of Marine Sponge-Derived Streptomyces spp. Isolates SM17 and SM18 With Their Closest Terrestrial Relatives Provides Novel Insights Into Environmental Niche Adaptations and Secondary Metabolite Biosynthesis Potential

Comparative Genomics of Marine Sponge-Derived Streptomyces spp. Isolates SM17 and SM18 With Their Closest Terrestrial Relatives Provides Novel Insights Into Environmental Niche Adaptations and Secondary Metabolite Biosynthesis Potential

Analysis of the complete genome sequence of a marine-derived strainStreptomycessp. S063 CGMCC 14582 reveals its biosynthetic potential to produce novel anti-complement agents and peptides

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

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