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The article presents the results of studying the biological characteristics (antagonistic and cellulase activity, antibiotic resistance, indolyl-3-acetic acid (IAC) production, the presence of polyketide synthase and cellulase genes) of 13 bacterial strains of the genus Streptomyces. The screening revealed a strain of Streptomyces sp. 2K10 with a high level of antifungal activity against the pathogen Fusarium petroliferatum; three strains (RPLN23, 1N8, 3N2) – antagonist of the causative agent of wheat septoria nodorum blotch (Parastagonospora nodorum). As a biocontrol agent of phytopathogens, the most promising strain among the studied streptomycetes is RPLN23, characterized by antifungal activity (diameter of inhibition zones 24–30 mm), the presence of PKS II genes (229 bp) and the ability to synthesize IAA. For biocontrol of bacterial and fungal pathogens, it is proposed to use the strain Streptomyces sp. 3N3. The work also revealed strains capable of effective destruction of carboxymethylcellulose (RPLN12, 2K9 and 3K9), and strains with genes encoding cellulases of the GH74 family (RSFN5, RPLN12, 3N2) in the genome. A number of streptomyces (RSFN5, RPLN5), which did not show antagonism to the studied cultures of fungi and bacteria, are at the same time interesting for the presence of the PKS II and GH74 genes. Most of the streptomyces studied in the work are sensitive to antibiotics of various groups: aminoglycosides, tetracycline, polypetides, chloramphenicols ansamycins and macrolides, but not β-lactams. The obtained data contribute to the disclosure of the potential of streptomyces for their practical use.

Abstract Background The excavation and utilization of endophytic fungi from medicinal plants is highly important for the development of new drugs. The endophytic fungus Aspergillus tamarii TPD11, which was isolated and obtained by the authors in the previous stage, can produce a variety of polyphyllins with important potential applications in hemostasis, inflammation and antitumor activities; however, the genomic information of TPD11 is still unknown. Results In this study, we sequenced and assembled the whole genome of the endophytic fungus A. tamarii TPD11, resolved the genome evolutionary relationships of 24 Aspergillus strains, and phylogenetic analysis of the genomes of 16 strains revealed the evolutionary differences between Aspergillus and Penicillium and the mechanisms of genome expansion and contraction. CAZy annotation analysis revealed that TPD11 obtains nutrients mainly by ingesting starch from the host plant. TPD11 has a biosynthesis-related gene cluster for the synthesis of squalestatin S1, and the silencing of this biosynthesis-related gene cluster might increase the content of polyphyllin. Annotation of 11 UDP-glycosyltransferase genes helps to further reveal the biosynthetic pathway of polyphyllin. In addition, secondary metabolism gene cluster and CAZy analyses confirmed the potential probiotic, insecticidal and antimicrobial activities of TPD11 on host plants. Conclusions This study reveals the intrinsic mechanism by which endophytic fungi increase the content of polyphyllin, which provides a basis for the synthetic synthesis of the natural product polyphyllin.

Background: The excavation and utilization of endophytic fungi from medicinal plants is highly important for the development of new drugs. The endophytic fungus Aspergillus tamarii TPD11, which was isolated and obtained by the authors in the previous stage, can produce a variety of polyphyllins with important potential applications in hemostasis, inflammation and antitumor activities; however, the genomic information of TPD11 is still unknown. Results: In this study, we sequenced and assembled the whole genome of the endophytic fungus A. tamarii TPD11, resolved the genome evolutionary relationships of 24 Aspergillus strains, and phylogenetic analysis of the genomes of 16 strains revealed the evolutionary differences between Aspergillus and Penicillium and the mechanisms of genome expansion and contraction. CAZy annotation analysis revealed that TPD11 obtains nutrients mainly by ingesting starch from the host plant. TPD11 has a biosynthesis-related gene cluster for the synthesis of squalestatin S1, and the silencing of this biosynthesis-related gene cluster might increase the content of polyphyllin. Annotation of 11 UDP-glycosyltransferase genes helps to further reveal the biosynthetic pathway of polyphyllin. In addition, secondary metabolism gene cluster and CAZy analyses confirmed the potential probiotic, insecticidal and antimicrobial activities of TPD11 on host plants. Conclusions: This study reveals the intrinsic mechanism by which endophytic fungi increase the content of polyphyllin, which provides a basis for the synthetic synthesis of the natural product polyphyllin. [ABSTRACT FROM AUTHOR]

Fungal secondary metabolites (SMs) represent an invaluable source of therapeutic drugs. Genomics-based approaches to SM discovery have revealed a vast and largely untapped biosynthetic potential within fungal genomes. Here, we used the publicly available fungal genome sequences from the NCBI public database, as well as tools such as antiSMASH, BIG-SLiCE, etc., to analyze a total of 11,598 fungal genomes, identifying 293,926 biosynthetic gene clusters (BGCs), which were subsequently categorized into 26,825 gene cluster families (GCFs). It was discovered that only a tiny fraction, less than 1%, of these GCFs could be mapped to known natural products (NPs). Some GCFs that only contain a single BGC internally are crucial for the biodiversity of fungal biosynthesis. Evident patterns emerged from our analysis, revealing popular taxa as prominent sources of both actual and potential biosynthetic diversity. Our study also suggests that the genus rank distribution of GCF is generally consistent with NP diversity. It is noteworthy that genera Xylaria, Hypoxylon, Colletotrichum, Diaporthe, Nemania, and Calonectria appear to possess a higher potential for SM synthesis. In addition, 7213 BGCs match possible known compound structures, and homologous gene clusters of well-known drugs can be located in different genera, facilitating the development of derivatives that share structural similarity to these drugs and may potentially possess similar biological activity. Our study demonstrated the various types of fungi with mining potential, assisting researchers in prioritizing their research efforts and avoiding duplicate mining of known resources to further explore fungal NP producers. [ABSTRACT FROM AUTHOR]

Abstract Background Volatile compounds are key elements in the interaction and communication between organisms at both interspecific and intraspecific levels. In complex bacterial communities, the emission of these fast-acting chemical messengers allows an exchange of information even at a certain distance that can cause different types of responses in the receiving organisms. The changes in secondary metabolism as a consequence of this interaction arouse great interest in the field of searching for bioactive compounds since they can be used as a tool to activate silenced metabolic pathways. Regarding the great metabolic potential that the Actinobacteria group presents in the production of compounds with attractive properties, we evaluated the reply the emitted volatile compounds can generate in other individuals of the same group. Results We recently reported that volatile compounds released by different streptomycete species trigger the modulation of biosynthetic gene clusters in Streptomyces spp. which finally leads to the activation/repression of the production of secondary metabolites in the recipient strains. Here we present the application of this rationale in a broader bacterial community to evaluate volatiles as signaling effectors that drive the activation of biosynthesis of bioactive compounds in other members of the Actinobacteria group. Using cocultures of different actinobacteria (where only the volatile compounds reach the recipient strain) we were able to modify the bacterial secondary metabolism that drives overproduction (e.g., granaticins, actiphenol, chromomycins) and/or de novo production (e.g., collismycins, skyllamycins, cosmomycins) of compounds belonging to different chemical species that present important biological activities. Conclusions This work shows how the secondary metabolism of different Actinobacteria species can vary significantly when exposed in co-culture to the volatile compounds of other phylum-shared bacteria, these effects being variable depending on strains and culture media. This approach can be applied to the field of new drug discovery to increase the battery of bioactive compounds produced by bacteria that can potentially be used in treatments for humans and animals.

Background: Volatile compounds are key elements in the interaction and communication between organisms at both interspecific and intraspecific levels. In complex bacterial communities, the emission of these fast-acting chemical messengers allows an exchange of information even at a certain distance that can cause different types of responses in the receiving organisms. The changes in secondary metabolism as a consequence of this interaction arouse great interest in the field of searching for bioactive compounds since they can be used as a tool to activate silenced metabolic pathways. Regarding the great metabolic potential that the Actinobacteria group presents in the production of compounds with attractive properties, we evaluated the reply the emitted volatile compounds can generate in other individuals of the same group. Results: We recently reported that volatile compounds released by different streptomycete species trigger the modulation of biosynthetic gene clusters in Streptomyces spp. which finally leads to the activation/repression of the production of secondary metabolites in the recipient strains. Here we present the application of this rationale in a broader bacterial community to evaluate volatiles as signaling effectors that drive the activation of biosynthesis of bioactive compounds in other members of the Actinobacteria group. Using cocultures of different actinobacteria (where only the volatile compounds reach the recipient strain) we were able to modify the bacterial secondary metabolism that drives overproduction (e.g., granaticins, actiphenol, chromomycins) and/or de novo production (e.g., collismycins, skyllamycins, cosmomycins) of compounds belonging to different chemical species that present important biological activities. Conclusions: This work shows how the secondary metabolism of different Actinobacteria species can vary significantly when exposed in co-culture to the volatile compounds of other phylum-shared bacteria, these effects being variable depending on strains and culture media. This approach can be applied to the field of new drug discovery to increase the battery of bioactive compounds produced by bacteria that can potentially be used in treatments for humans and animals. [ABSTRACT FROM AUTHOR]

Actinomycetes are remarkable natural sources of active natural molecules and enzymes of considerable industrial value. Streptomyces mobaraensis is the first microorganism found to produce transglutaminase with broad industrial applications. Although transglutaminase in S. mobaraensis has been well studied over the past three decades, the genome of S. mobaraensis and its secondary metabolic potential were poorly reported. Here, we presented the complete genome of S. mobaraensis DSM40587 obtained from the German Collection of Microorganisms and Cell Cultures GmbH. It contains a linear chromosome of 7,633,041 bp and a circular plasmid of 23,857 bp. The chromosome with an average GC content of 73.49% was predicted to harbour 6683 protein-coding genes, seven rRNA and 69 tRNA genes. Comparative genomic analysis reveals its meaningful genomic characterisation. A comprehensive bioinformatics investigation identifies 35 putative BGCs (biosynthesis gene clusters) involved in synthesising various secondary metabolites. Of these, 13 clusters showed high similarity (> 55%) to known BGCs coding for polyketides, nonribosomal peptides, hopene, RiPP (Ribosomally synthesized and post-translationally modified peptides), and others. Furthermore, these BGCs with over 65% similarity to the known BGCs were analysed in detail. The complete genome of S. mobaraensis DSM40587 reveals its capacity to yield diverse bioactive natural products and provides additional insights into discovering novel secondary metabolites. [ABSTRACT FROM AUTHOR]

Microbial natural products are important for the understanding of microbial interactions, chemical defense and communication, and have also served as an inspirational source for numerous pharmaceutical drugs. Tropical marine cyanobacteria have been highlighted as a great source of new natural products, however, few reports have appeared wherein a multi-omics approach has been used to study their natural products potential (i.e., reports are often focused on an individual natural product and its biosynthesis). This study focuses on describing the natural product genetic potential as well as the expressed natural product molecules in benthic tropical cyanobacteria. We collected from several sites around the world and sequenced the genomes of 24 tropical filamentous marine cyanobacteria. The informatics program antiSMASH was used to annotate the major classes of gene clusters. BiG-SCAPE phylum-wide analysis revealed the most promising strains for natural product discovery among these cyanobacteria. LCMS/MS-based metabolomics highlighted the most abundant molecules and molecular classes among 10 of these marine cyanobacterial samples. We observed that despite many genes encoding for peptidic natural products, peptides were not as abundant as lipids and lipopeptides in the chemical extracts. Our results highlight a number of highly interesting biosynthetic gene clusters for genome mining among these cyanobacterial samples.

Introduction: Although Bacillus species have produced a wide variety of structurally diverse and biologically active natural products, the secondary biosynthetic potential of Bacillus species is widely underestimated due to the limited number of biosynthetic gene clusters (BGCs) in this genus. The significant variation in the diversity and novelty of BGCs across different species within the Bacillus genus presents a major obstacle to the efficient discovery of novel natural products from Bacillus. Methods: In this study, the number of each class of BGCs in all 6,378 high-quality Bacillus genomes was predicted using antiSMASH, the species-specificity of BGC distribution in Bacillus was investigated by Principal component analysis. Then the structural diversity and novelty of the predicted secondary metabolites in Bacillus species with specific BGC distributions were analyzed using molecular networking. Results: Our results revealed a certain degree of species-specificity in the distribution of BGCs in Bacillus, which was mainly contributed by siderophore, type III polyketide synthase (T3PKS), and transAT-PKS BGCs. B. wiedmannii, B. thuringiensis, and B. cereus are rich in RiPP-like and siderophore BGCs, but lack T3PKS BGCs, while B. amyloliquefaciens and B. velezensis are abundant in transAT-PKS BGCs. These Bacillus species collectively encode 77,541 BGCs, with NRPS and RiPPs being the two most dominant types, which are further categorized into 4,291 GCFs. Remarkably, approximately 54.5% of GCFs and 93.8% of the predicted metabolite scaffolds are found exclusively in a single Bacillus species. Notably, B. cereus, B. thuringiensis, and B. velezensis exhibit the highest potential for producing species-specific NRPS and PKS bioinformatic natural products. Taking two species-specific NRPS gene clusters as examples, the potential of Bacillus to synthesize novel species-specific natural products is illustrated. Conclusion: This study highlights the species-specificity of the secondary biosynthetic potential in Bacillus and provides valuable insights for the targeted discovery of novel natural products from this genus. [ABSTRACT FROM AUTHOR]

Mangrove rhizosphere soils host diverse Actinobacteria tolerant to numerous stresses and are inevitably capable of exhibiting excellent biological activity by producing impressive numbers of bioactive natural products, including those with potential medicinal applications. In this study, we applied an integrated strategy of combining phylogenetic diversity, biological activities, and biosynthetic gene clusters (BGCs) screening approach to investigate the biotechnological importance of Actinobacteria isolated from mangrove rhizosphere soils from Hainan Island. The actinobacterial isolates were identifified using a combination of colony morphological characteristics and 16S rRNA gene sequence analysis. Based on the results of PCR-detected BGCs screening, type I and II polyketide synthase (PKS) and non-ribosomal synthetase (NRPS) genes were detected. Crude extracts of 87 representative isolates were subjected to antimicrobial evaluation by determining the minimum inhibitory concentration of each strain against six indicator microorganisms, anticancer activities were determined on human cancer cell lines HepG2, HeLa, and HCT-116 using an MTT colorimetric assay, and immunosuppressive activities against the proliferation of Con A-induced T murine splenic lymphocytes in vitro. A total of 287 actinobacterial isolates affiliated to 10 genera in eight families of six orders were isolated from five different mangrove rhizosphere soil samples, specififically, Streptomyces (68.29%) and Micromonospora (16.03%), of which 87 representative strains were selected for phylogenetic analysis. The crude extracts of 39 isolates (44.83%) showed antimicrobial activity against at least one of the six tested indicator pathogens, especially ethyl acetate extracts of A-30 (Streptomyces parvulus), which could inhibit the growth of six microbes with MIC values reaching 7.8 μg/mL against Staphylococcus aureus and its resistant strain, compared to the clinical antibiotic ciproflfloxacin. Furthermore, 79 crude extracts (90.80%) and 48 (55.17%) of the isolates displayed anticancer and immunosuppressive activities, respectively. Besides, four rare strains exhibited potent immunosuppressive activity against the proliferation of Con A-induced T murine splenic lymphocyte in vitro with an inhibition rate over 60% at 10 μg/mL. Type I and II polyketide synthase (PKS) and non-ribosomal synthetase (NRPS) genes were detected in 49.43, 66.67, and 88.51% of the 87 Actinobacteria, respectively. Signifificantly, these strains (26 isolates, 29.89%) harbored PKS I, PKS II, and NRPS genes in their genomes. Nevertheless, their bioactivity is independent of BGCs in this study. Our findings highlighted the antimicrobial, immunosuppressive, and anticancer potential of mangrove rhizosphere Actinobacteria from Hainan Island and the biosynthetic prospects of exploiting the corresponding bioactive natural product. [ABSTRACT FROM AUTHOR]

YP6 was isolated from Triticum aestivum L. seeds and YBS14 was isolated from the roots of Helichrysum italicum L. Partial sequence analysis of ITS5-5.8-ITS4 region of the nuclear ribosomal DNA with universal primers identified YP6 as Pichia fermentans and YBS14 as Saccharomyces cerevisiae. Both yeast strains produced indole-3-acetic acid when cultivated in a medium supplemented with 0.2 % L-tryptophan. The antimicrobial activity of yeast strains against plant pathogenic fungi was determined. YP6 and YBS14 were tested for endophytic colonization of Solanaceae plants by soil drenching and leaf spraying. To establish colonization in the various tissues of tested plants, samples were taken and explants were inoculated on yeast malts agar. The effect of the microbial endophytes on photosynthesis, stomatal conductivity, and transpiration intensity was analyzed by using the portable photosynthetic system for CO2 analysis in plants. In all treated plants photosynthesis was intense and growth stimulation was observed. The final aim of the present study is to evaluate endophytic yeast and demonstrate their PGP activity. [ABSTRACT FROM AUTHOR]

Inonotus hispidus mushroom is a traditional medicinal fungus with anti-cancer, antioxidation, and immunomodulatory activities, and it is used in folk medicine as a treatment for indigestion, cancer, diabetes, and gastric illnesses. Although I. hispidus is recognized as a rare edible medicinal macrofungi, its genomic sequence and biosynthesis potential of secondary metabolites have not been investigated. In this study, using Illumina NovaSeq combined with the PacBio platform, we sequenced and de novo assembled the whole genome of NPCB_001, a wild I. hispidus isolate from the Aksu area of Xinjiang Province, China. Comparative genomic and phylogenomic analyses reveal interspecific differences and evolutionary traits in the genus Inonotus. Bioinformatics analysis identified candidate genes associated with mating type, polysaccharide synthesis, carbohydrate-active enzymes, and secondary metabolite biosynthesis. Additionally, molecular networks of metabolites exhibit differences in chemical composition and content between fruiting bodies and mycelium, as well as association clusters of related compounds. The deciphering of the genome of I. hispidus will deepen the understanding of the biosynthesis of bioactive components, open the path for future biosynthesis research, and promote the application of Inonotus in the fields of drug research and functional food manufacturing. [ABSTRACT FROM AUTHOR]

Streptomyces FIM95-F1, an actinomycete originating from mangroves of Quanzhou bay, exhibits the capability to produce the antifungal antibiotic scopafungin. Here, the complete genome of Streptomyces sp. FIM95-F1 is presented with a GC content of 71.04 %, comprising a 9,718,239-bp linear chromosome, 8236 protein-coding genes, 18 rRNA genes, 64 tRNA genes, 2 prophages, and 58 CRISPR regions. In silico analysis revealed the presence of 42 biosynthetic gene clusters (BGCs), the majority of which demonstrated similarity to both known and novel BGCs responsible for the biosynthesis of previously known and novel bioactive agents of microbial origin. A comprehensive comparison between the scopafungin BGC and niphimycin BGC has indicated a potential shared pathway for the biosynthesis of scopafungin. One of the intriguing findings of this study was the discovery of at least two novel BGCs (namely Cluster 26 and Cluster 32) present within biosynthetic gene clusters. Our findings suggest that Streptomyces sp. FIM95-F1 possesses significant potential in producing a diverse array of both known and novel bioactive compounds, which could be valuable in the field of drug discovery., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

ABSTRACT The prevalence of superbugs, represented by methicillin-resistant Staphylococcus aureus (MRSA), has become a serious clinical and public safety concern with rising incidence in hospitals. Polyketides with diverse chemical structures harbor many antimicrobial activities, including those of rifampin and rapamycin against MRSA. Streptomyces sp. QHH-9511 was isolated from a niche habitat in the Qinghai-Tibet Plateau and used to produce antibacterial metabolites. Herein, an integrated approach combining genome mining and metabolic analysis were employed to decipher the chemical origin of the antibacterial components with pigmented properties in strain QHH-9511, a novel Streptomyces species from a lichen symbiont on the Qinghai-Tibet Plateau. Genomic phylogeny assembled at the chromosome level revealed its unique evolutionary state. Further genome mining uncovered 36 candidate gene clusters, most of which were uncharacterized. Meanwhile, based on liquid chromatography coupled to diode array detection mass spectrometry, a series of granaticins, BSMs, chromones, phaeochromycins, and related molecules were discovered by using the Global Natural Product Social molecular networking platform. Subsequently, several pigment compounds were isolated and identified by high-resolution mass spectrometry and/or nuclear magnetic resonance, among which the structure-activity relationships of seven aromatic polyketides showed that the fused lactone ring of the C-2 carboxyl group could increase antibacterial activity. Genetic experiments indicated that all seven aromatic polyketides are a series of metabolic shunts produced by a single type II polyketide synthase (PKS) cluster. Comparative genomic analysis of granaticin producers showed that the granaticin gene cluster is widely distributed. This study provides an efficient method to combine genome mining and metabolic profiling techniques to uncover bioactive metabolites derived from specific habitats, while deepening our understanding of aromatic polyketide biosynthesis. IMPORTANCE Undescribed microorganisms from special habitats are being screened for anti-superbug drug molecules. In a project to screen actinomycetes for anti-MRSA activity, we isolated a Streptomyces strain from Qinghai Lake lichens. The phylogeny based on the genome assembled at the chromosome level revealed this strain's unique evolutionary state. The chemical origins of the antibacterial components with pigment properties in strain QHH-9511 were determined using an integrated approach combining genome mining and metabolic analysis. Further genome mining uncovered 36 secondary metabolite gene clusters, the majority of which were previously unknown. A series of aromatic compounds were discovered using molecular network analysis, separation, and extraction. Genetic experiments revealed that all seven aromatic polyketides are a series of metabolic shunts produced by a single cluster of type II PKSs. This study describes a method for identifying novel Streptomyces from specific habitats by combining genome mining with metabolic profiling techniques.

The increasing appearance of multiresistant pathogens, as well as emerging diseases, has highlighted the need for new strategies to discover natural compounds that can be used as therapeutic alternatives, especially in the genus Streptomyces, which is one of the largest producers of bioactive metabolites. In recent years, the study of volatile compounds (VOCs) has raised interest because of the variety of their biological properties in addition to their involvement in cell communication. In this work, we analyze the implications of VOCs as mediating molecules capable of inducing the activation of biosynthetic pathways of bioactive compounds in surrounding Actinomycetes. For this purpose, several strains of Streptomyces were co-cultured in chamber devices that allowed VOC exchange while avoiding physical contact. In several of those strains, secondary metabolism was activated by VOCs emitted by companion strains, resulting in increased antibiotic production and synthesis of new VOCs. This study shows a novel strategy to exploit the metabolic potential of Actinomycetes as well as emphasizes the importance of studying the interactions between different microorganisms sharing the same ecological niche. [ABSTRACT FROM AUTHOR]

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We investigated the biosynthetic potential of soil-associated actinobacteria originating from Indonesia, identified as Streptomyces luridus and as Streptomyces luteosporeus. Antimicrobial assays indicated inhibitory activity by both strains against the pathogen Pseudomonas aeruginosa, with S. luteosporeus particularly inhibiting the growth of Bacillus subtilis. PCR-amplification, cloning, and sequencing of ketosynthase (KS) domains of type I modular polyketide (PKS-I) and adenylation (AD) domains of non-ribosomal peptide synthetase (NRPS) indicated the diversity of KS and AD domains derived from both Indonesian Streptomyces. Further phylogenetic analysis showed that KS domains from the subclass cis-AT PKS can be classified as being a part of a loading module or an extension module, along with their predicted substrate specificity. The results suggest that both strains are a potential source of novel biosynthetic pathways. This genetic analysis approach can be used as a fast guide to obtain insight into natural product biosynthetic gene diversity in microorganisms.

ABSTRACT Laetiporus sulphureus mushroom is a complementary and alternative medicine that has anticancer, antioxidation, and analgesic effects and immunomodulatory activity; it is used as a treatment for cough and rheumatism and is a functional food that can improve physical fitness. Even though L. sulphureus has garnered considerable biotechnological and pharmacological interest due to its excellent cellulose-degrading ability and diverse biological activities, its biosynthetic potential regarding polysaccharides and secondary metabolites has not been thoroughly examined. In this study, we sequenced and assembled the whole genome of a wild L. sulphureus isolate, NWAFU-1, from the Qinling Mountains in China. Comparative genomes analysis revealed genomic differences between subspecies, and phylogenomic analysis revealed evolutionary divergence as well as genome expansion and contraction of individual Polyporaceae family species. Bioinformatics investigation identified candidate genes associated with mating type, polysaccharide synthesis, carbohydrate-active enzymes, and secondary-metabolite biosynthesis, which included multiple terpenoids, nonribosomal peptides, and polyketides. The locations of biosynthetic core genes were mapped and displayed on chromosomes and contigs. Totals of 143 proteins from 126 coding genes were identified and divided into 14 cytochrome P450 families. Furthermore, the biosynthetic network of tetracyclic triterpenoid active components was postulated by genome mining of related genes combined with the molecular network of metabolites. The genome analysis of L. sulphureus in this study improves the understanding of the biosynthesis of active compounds, which will lay a theoretical foundation for subsequent research on active-compound biosynthesis and promote the application of Laetiporus in the field of drug research and functional-food creation. IMPORTANCE L. sulphureus is a parasitic basidiomycete fungus that causes brown rot. The fruiting bodies of L. sulphureus are used as ancient medicines in China and Europe to cure cancer, analgesia, cough, and rheumatism and are considered a functional food that regulates the body and improves health. L. sulphureus was inferred to be a tetrapolar system based on a high-quality genome, which will aid molecular breeding and artificial farming. Screening polysaccharide synthesis candidate genes and comparing carbohydrate-associated genes in brown-rot basidiomycetes help understand their growth. Identifying core genes for secondary-metabolite biosynthesis, gene cluster family analysis, and comparative cluster analysis will guide heterologous-biosynthesis investigations of these genes and help elucidate the biosynthetic pathways for L. sulphureus bioactive natural components. The biosynthesis network of tetracyclic triterpenes was mapped using metabolite profiling and genome scanning. This work explores the biosynthetic capacity of L. sulphureus-derived natural products and lays the foundation for biosynthetic studies of them.

Aspergillus niger is one of the most important sources of secondary metabolites (SMs), with a wide array of pharmacological effects, including anti-inflammatory, antitumor, immunomodulatory and antioxidant effects. However, the biosynthetic analysis of these bioactive components has been rarely reported owing to the lack of high-quality genome sequences and comprehensive analysis. In this study, the whole genome of one marine-sponge-derived strain A. niger L14 was sequenced and assembled as well as in-depth bioinformatic analysis. The results indicated that the sequence assembly of strain L14 generated one high-quality genome with a total size of 36.1 Mb, a G + C content of 45.3% and an N50 scaffold of 4.2 Mb. Gene annotation was extensively deployed using various BLAST databases, including non-redudant (Nr) protein sequence, nucleotide (Nt) sequence, Swiss-Prot, Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and Clusters of Orthologous Groups (COG) as well as Pathogen Host Interactions (PHI) and Carbohydrate-active enzymes (CAZy) databases. AntiSMASH analysis revealed that this marine strain harbors a total of 69 SMs biosynthesis gene clusters (BGCs), including 17 PKSs, 18 NRPSs, 21 NRPS-likes, 9 terpenes, 2 indoles, 1 betalactone and 1 siderophore, suggesting its biosynthetic potential to produce a wide variety of SMs. These findings will assist in future investigations on the genetic basis of strain L14 and provide insights into its new bioactive SMs for new drug discovery. [ABSTRACT FROM AUTHOR]

Marine actinomycetes are an important source of antibiotics, but many of them are yet to be explored in terms of taxonomy, ecology, and functional activity. In this study, two marine actinobacterial strains, designated SCSIO 64649T and SCSIO 03032, were isolated, and the potential for bioactive natural product discovery was evaluated based on genome mining, compound detection, and antimicrobial activity. Phylogenetic analysis of the 16S rRNA gene sequences showed that strain SCSIO 64649T formed a single clade with SCSIO 03032 (similarity 99.5%) and sister clades with the species Streptomyces specialis DSM 41924T (97.1%) and Streptomyces manganisoli MK44T (96.8%). The whole genome size of strain SCSIO 64649T was 6.63 Mbp with a 73.6% G + C content. The average nucleotide identity and digital DNA–DNA hybridization between strain SCSIO 64649T and its closest related species were well below the thresholds recommended for species delineation. Therefore, according to the results of polyphasic taxonomy analysis, the strains SCSIO 64649T and SCSIO 03032 are proposed to represent a novel species named Streptomyces marincola sp. nov. Furthermore, strains SCSIO 64649T and 03032 encode 37 putative biosynthetic gene clusters, and in silico analysis revealed that this new species has a high potential to produce unique natural products, such as a novel polyene polyketide compounds, two mayamycin analogs, and a series of post-translationally modified peptides. In addition, other important bioactive natural products, such as heronamide F, piericidin A1, and spiroindimicin A, were also detected in strain SCSIO 64649T. Finally, this new species' metabolic crude extract showed a strong antimicrobial activity. Thanks to the integration of all these analyses, this study demonstrates that the novel species Streptomyces marincola has a unique and novel secondary metabolite biosynthetic potential that not only is beneficial to possible marine hosts but that could also be exploited for industrial applications. [ABSTRACT FROM AUTHOR]

Marine actinomycetes are an important source of antibiotics, but many of them are yet to be explored in terms of taxonomy, ecology, and functional activity. In this study, two marine actinobacterial strains, designated SCSIO 64649T and SCSIO 03032, were isolated, and the potential for bioactive natural product discovery was evaluated based on genome mining, compound detection, and antimicrobial activity. Phylogenetic analysis of the 16S rRNA gene sequences showed that strain SCSIO 64649T formed a single clade with SCSIO 03032 (similarity 99.5%) and sister clades with the species Streptomyces specialis DSM 41924T (97.1%) and Streptomyces manganisoli MK44T (96.8%). The whole genome size of strain SCSIO 64649T was 6.63 Mbp with a 73.6% G + C content. The average nucleotide identity and digital DNA–DNA hybridization between strain SCSIO 64649T and its closest related species were well below the thresholds recommended for species delineation. Therefore, according to the results of polyphasic taxonomy analysis, the strains SCSIO 64649T and SCSIO 03032 are proposed to represent a novel species named Streptomyces marincola sp. nov. Furthermore, strains SCSIO 64649T and 03032 encode 37 putative biosynthetic gene clusters, and in silico analysis revealed that this new species has a high potential to produce unique natural products, such as a novel polyene polyketide compounds, two mayamycin analogs, and a series of post-translationally modified peptides. In addition, other important bioactive natural products, such as heronamide F, piericidin A1, and spiroindimicin A, were also detected in strain SCSIO 64649T. Finally, this new species’ metabolic crude extract showed a strong antimicrobial activity. Thanks to the integration of all these analyses, this study demonstrates that the novel species Streptomyces marincola has a unique and novel secondary metabolite biosynthetic potential that not only is beneficial to possible marine hosts but that could also be exploited for industrial applications.

Antarctic actinobacteria, which can be isolated from both soils and marine sediments, demonstrate a wide range of antimicrobial activities as well as significant biosynthetic potential as the producers of biologically active compounds. However, the actinobacterial diversity of the Antarctic region has not yet been sufficiently studied. The present study sought to examine the diversity and antibacterial activity of culturable actinobacteria isolated from the rhizosphere soil of Deschampsia antarctica (É. Desv.), which was collected from Galindez Island, Maritime Antarctic. Among the actinobacteria isolated using a 16S rRNA gene sequence-based phylogenetic analysis process, five genera, namely Streptomyces, Micromonospora, Umezawaea, Kribbella and Micrococcus, were identified. To the best of our knowledge, this is the first report to describe the isolation and initial characterisation of members of the genus Umezawaea from the Antarctic. The isolated actinobacteria were assayed to determine their activity against Gram-positive bacteria, Gram-negative bacteria and yeast. Among the isolated strains, only 30.2% were able to inhibit the growth of at least one of the tested pathogens. The polymerase chain reaction-based screening of the biosynthetic genes revealed the presence of type I polyketide synthases (65.1%), type II polyketide synthases (25.6%) and non-ribosomal peptide synthetases (9.3%) in the actinobacteria strains. The examination of the sensitivity/resistance to antibiotics profile of the actinobacteria strains revealed their high sensitivity in relation to the tested antibiotics. Taken together, the results showed that Antarctic actinobacteria demonstrate potential as the producers of natural bioactive compounds, which means that they represent a valuable prospect for further studies. [ABSTRACT FROM AUTHOR]

Проблематика. Актуальними проблемами людства сьогодні є висока частота виникнення нових мульти­резистентних форм патогенних мікроорганізмів, нестача продуктів харчування, а також забруднення навколишнього середовища, особливо агроекоситем. Скринінг нових природних продуктів та впровадження їх у медицині, ветеринарії, сільському господарстві тощо є одним із підходів до вирішення цих проблем. Особливий інтерес викликають актиноміцети – рекордсмени за кількістю синтезованих біологічно активних сполук. Мета. Метою роботи є оцінка біосинтетичних властивостей актиноміцетів ризосфери ендеміка Кримського півострова сонянки Cтевена Helianthemum stevenii Rupr. Ex Juz. & Pozd. Методика реалізації. Зразки ризосфери H. stevenii Rupr. Ex Juz. & Pozd. відбирали на південних схилах Нікітського хребта (Кримський півострів). Виділяли актиноміцети прямим посівом змивів ризосфери, обробкою коренів водним розчином фенолу або прожарюванням їх за 100 °С протягом 60 хв з подальшим висіванням на живильні середовища. Антибактерійні та протикандидозну активності вивчали через висівання культур актиноміцетів уколом на вівсяне середовище і заливання 0,7 %-ним агаром з певною тест-культурою. Антифунгальні властивості вивчали через викладання агарового блоку з 5-денною культурою гриба на чашки з 3-денними культурами актиноміцетів та подальшим інкубуванням протягом 4-х діб. За відношенням діаметра зон пригнічення росту тест-культур до діаметра колоній актиноміцетів визначали індекс активності (ІА). Фітостимулювальні та фер­ментативні властивості вивчали загальноприйнятими методами. Результати. З ризосфери H. stevenii Rupr. Ex Juz. & Pozd. виділено 107 штамів актиноміцетів. 23,2 % ізолятів пригнічували ріст одного і більше типових штамів мікроорганізмів, здатних спричинювати інфекції людини. 8,4 % штамів актиноміцетів були антагоністами S. аureus, ріст грамнегативних бактерій затримувало значно менше досліджуваних культур. ІА цих ізолятів не перевищував 3. 80,1 % ізолятів були антагоністами хоча б одного штаму фітопатогенних бактерій. ІА цих штамів становив 1,2–13,0. Антифунгальну активність виявляло 15,9 % ізолятів, а їх ІА не перевищував 3. 17,8 % штамів продукували індоліл-3-оцтову кислоту, 10,3 % – сидерофори, а 14,2 % солюбілізували сполуки фосфору. Значна частка штамів актиноміцетів продукували гідролітичні ферменти: амілази, ліпази, пектинази, протеази. 29,9 % ізолятів здатні деколоризувати Azure B, а також 8,4 % штамів актиноміцетів синтезували лакази. Висновки. Оцінено здатність актиноміцетів ризосфери Helianthemum stevenii Rupr. Ex Juz. & Pozd синтезувати антимікробні речовини, ферменти, а також сполуки, здатні сприяти росту і розвитку рослин. Виділено штами з широким спектром антимікробної дії, а також штами, які специфічно пригнічували ріст певного штаму патогенних мікроорганізмів. Для низки антагоністів фіто­патоген­ної мікрофлори була притаманна фітостимулювальна дія. Виділено продуцентів гідролаз та оксидоредуктаз.

Marine environments are home to an extensive number of microorganisms, many of which remain unexplored for taxonomic novelty and functional capabilities. In this study, a slow-growing Streptomyces strain expressing unique genomic and phenotypic characteristics, P38-E01T, was described using a polyphasic taxonomic approach. This strain is part of a collection of over 8,000 marine Actinobacteria isolates collected in the Trondheim fjord of Norway by SINTEF Industry (Trondheim, Norway) and the Norwegian University of Science and Technology (NTNU, Trondheim, Norway). Strain P38-E01T was isolated from the sediments of the Trondheim fjord, and phylogenetic analyses affiliated this strain with the genus Streptomyces, but it was not closely affiliated with other described species. The closest related type strains were Streptomyces daliensis YIM 31724T (98.6%), Streptomyces rimosus subsp. rimosus ATCC 10970T (98.4%), and Streptomyces sclerotialus NRRL ISP-5269T (98.3%). Predominant fatty acids were C16:0 iso, C16:0, and Summed Feature 3, and the predominant respiratory quinones were MK-10(H6), MK-10(H4), and MK9(H4). The main polar lipids were identified as diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol, and phosphoglycolipid. The whole-cell sugars were glucose, ribose, and in minor amounts, mannose. The cell wall peptidoglycan contained LL-diaminopimelic acid. The draft genome has a size of 6.16 Mb, with a %G + C content of 71.4% and is predicted to contain at least 19 biosynthetic gene clusters encoding diverse secondary metabolites. Strain P38-E01T was found to inhibit the growth of the pathogenic yeast Candida albicans ATCC 90028 and a number of Gram-positive bacterial human and plant pathogens. Metabolites extracted from cultures of P38-E01T were analyzed by mass spectrometry, and it was found that the isolate produced the antifungal compound candicidin. Phenotypic and chemotaxonomic signatures, along with phylogenetic analyses, distinguished isolate P38-E01T from its closest neighbors; thus, this isolate represents a novel species of the genus Streptomyces for which the name Streptomyces tardus sp. nov. (P38-E01T = CCM 9049T = DSM 111582T) is proposed.

Marine environments are home to an extensive number of microorganisms, many of which remain unexplored for taxonomic novelty and functional capabilities. In this study, a slow-growing Streptomyces strain expressing unique genomic and phenotypic characteristics, P38-E01 T , was described using a polyphasic taxonomic approach. This strain is part of a collection of over 8,000 marine Actinobacteria isolates collected in the Trondheim fjord of Norway by SINTEF Industry (Trondheim, Norway) and the Norwegian University of Science and Technology (NTNU, Trondheim, Norway). Strain P38-E01 T was isolated from the sediments of the Trondheim fjord, and phylogenetic analyses affiliated this strain with the genus Streptomyces , but it was not closely affiliated with other described species. The closest related type strains were Streptomyces daliensis YIM 31724 T (98.6%), Streptomyces rimosus subsp. rimosus ATCC 10970 T (98.4%), and Streptomyces sclerotialus NRRL ISP-5269 T (98.3%). Predominant fatty acids were C16:0 iso, C16:0, and Summed Feature 3, and the predominant respiratory quinones were MK-10(H6), MK-10(H4), and MK9(H4). The main polar lipids were identified as diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol, and phosphoglycolipid. The whole-cell sugars were glucose, ribose, and in minor amounts, mannose. The cell wall peptidoglycan contained LL-diaminopimelic acid. The draft genome has a size of 6.16 Mb, with a %G + C content of 71.4% and is predicted to contain at least 19 biosynthetic gene clusters encoding diverse secondary metabolites. Strain P38-E01 T was found to inhibit the growth of the pathogenic yeast Candida albicans ATCC 90028 and a number of Gram-positive bacterial human and plant pathogens. Metabolites extracted from cultures of P38-E01 T were analyzed by mass spectrometry, and it was found that the isolate produced the antifungal compound candicidin. Phenotypic and chemotaxonomic signatures, along with phylogenetic analyses, distinguished isolate P38-E01 T from its closest neighbors; thus, this isolate represents a novel species of the genus Streptomyces for which the name Streptomyces tardus sp. nov. (P38-E01 T = CCM 9049 T = DSM 111582 T ) is proposed. [ABSTRACT FROM AUTHOR]

This research work aimed at investigating the chemistry and biosynthetic potential of ascidian-associated symbionts that originated from Manado Bay, North Sulawesi. We initially enriched the symbiotic cells associated with the Manadonese ascidian Lissoclinum patella. Subsequently we identified the presence of Prochloron didemni in both unenriched and salt-enriched samples by examining the 16S rRNA gene and the chlorophyll A oxygenase (CAO) gene. Investigation of the secondary metabolites by HPLC, LCMS/MS, and NMR showed the presence of ulithiacyclamide along with patellamide E in the unenriched symbiotic cells. Interestingly, ulithiacyclamide was detected in the enriched cells from the same Ascidian specimen. Molecular docking showed the high binding affinity of both compounds to estrogen receptor beta (ER-β) protein. This is a subtype of the nuclear receptor superfamily expressed abnormally in ovarian cancer cells. Furthermore, we isolated a patE gene variant encoding for a precursor with patellamide E (VTVCITFC) and ulithiacyclamide (CTLCCTLC) core peptides from the enriched cells. This represents a new core peptide combination. The outcome of this work provides a basis for producing useful cyclic peptides, in sustainable way, through symbiont cultivation. This could become a platform for bioengineering to generate diverse compound analogues. [ABSTRACT FROM AUTHOR]

Beehives are populated by bacterial species with a protective role against honey bee pathogens thanks to the production of bioactive metabolites. These compounds are largely unexploited despite their high potential interest for pest management. This study evaluated the capability of bacterial species associated with honey bees to produce 2-heptanone, a volatile organic compound with anesthetic properties of the parasitic mite Varroa destructor. The production of this compound was quantified by SPME-GC-MS in a culture filtrate of nine bacterial strains isolated from the surface of honey bees, and the biosynthetic potential was evaluated in bacterial species associated with apiaries by searching for protein homologs putatively involved in its biosynthesis by using biocomputational tools. The findings pointed out that 2-heptanone was produced by Acetobacteraceae bacterium, Bacillus thuringiensis and Apilactobacillus kunkeei isolates in concentrations between 1.5 and 2.6 ng/mL and that its production was strain-specific. Putative methylketone synthase homologs were found in Bacillus, Gilliamella, Acetobacteraceae, Bartonella and Lactobacillaceae, and the protein sequence results were distributed in nine Sequence Similarity Network (SSN) clusters. These preliminary results support the hypothesis that 2-heptanone may act as a mediator of microbial relationships in hives and provide contributions to assess the role and biosynthetic potential of 2-heptanone in apiaries.

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.

Microbial natural products are important for the understanding of microbial interactions, chemical defense and communication, and have also served as an inspirational source for numerous pharmaceutical drugs. Tropical marine cyanobacteria have been highlighted as a great source of new natural products, however, few reports have appeared wherein a multi-omics approach has been used to study their natural products potential (i.e., reports are often focused on an individual natural product and its biosynthesis). This study focuses on describing the natural product genetic potential as well as the expressed natural product molecules in benthic tropical cyanobacteria. We collected from several sites around the world and sequenced the genomes of 24 tropical filamentous marine cyanobacteria. The informatics program antiSMASH was used to annotate the major classes of gene clusters. BiG-SCAPE phylum-wide analysis revealed the most promising strains for natural product discovery among these cyanobacteria. LCMS/MS-based metabolomics highlighted the most abundant molecules and molecular classes among 10 of these marine cyanobacterial samples. We observed that despite many genes encoding for peptidic natural products, peptides were not as abundant as lipids and lipopeptides in the chemical extracts. Our results highlight a number of highly interesting biosynthetic gene clusters for genome mining among these cyanobacterial samples.

Zainal Abidin, Z.A.; Chowdhury, A.J.K.; Abdul Malek, N., and Zainuddin, Z., 2018. Diversity, antimicrobial capabilities, and biosynthetic potential of mangrove actinomycetes from coastal waters in Pahang, Malaysia. In: Ashraf, M.A. and Chowdhury, A.J.K. (eds.), Coastal Ecosystem Responses to Human and Climatic Changes throughout Asia. Actinomycetes are biotechnologically important for their unparalleled capability to produce various bioactive secondary metabolites. The diversity and antimicrobial capabilities were investigated for actinomycetes, which were previously isolated from mangrove sediment of the Pahang mangrove forest. The biosynthetic potential using type I polyketide synthase (PKS-I) and nonribosomal peptide synthetase (NRPS) genes and the morphological characteristics of actinomycetes were also determined. Representative isolates were selected from five sampling locations in the Kuantan mangrove forest. Antimicrobial activities of crude ethyl acetate extract of these actinomycetes against five test microorganisms—Bacillus subtilis, Candida albicans, Escherichia coli, Serratia marcescens, and Staphylococcus aureus—were evaluated using the disc diffusion method. Actinomycetes were identified using the 16S rRNA gene sequence, and culture characteristics of selected actinomycetes were determined by inoculating the strains onto a set of agar media, namely, starch–yeast extract agar, inorganic salt–starch agar, starch–casein agar, and nutrient agar. Screening of the biosynthetic potential of these actinomycetes was achieved through polymerase chain reaction amplification of PKS-I and NRPS genes. Most isolates exhibited moderate to good antimicrobial activities toward B. subtilis and S. aureus, and a few inhibited C. albicans and E. coli. Streptomyces sp. K1-01 and Streptomyces sp. K2-03 showed antimicrobial activity against all test organisms, suggesting a broad-spectrum nature of the compounds they produced. Mangrove actinomycetes enumerated in this study demonstrated a high level of diversity, and they were distributed among nine genera. Streptomyces and Micromonospora were the most predominant genera observed, alongside Micrococcus, Gordonia, Nocardia, Dietzia, Pseudonocardia, Saccharopolyspora, and Verrucosispora. However, there is no direct correlation between antimicrobial capability and presence of PKS-I and NRPS in actinomycetes. Cultural characterization of selected actinomycetes revealed two interesting isolates— Micromonospora sp. K3-13, producing blue diffusible pigment, and Streptomyces sp. K2-03, producing purple diffusible pigment. This study demonstrated the potential of mangrove sediment as a new resource for highly diverse actinomycetes with biosynthetic capabilities. Detection of PKS-I and NRPS in these actinomycetes helps to establish a focus group that can be applied for future study of the natural product, particularly in antibiotic production. [ABSTRACT FROM AUTHOR]

Microbial natural products and their structural analogues have widely used as pharmaceutical agents, especially for infectious diseases and cancer. Despite this success, new structural classes with innovative chemistry and modes of action are urgently needed to be developed to combat the growing antimicrobial resistance and other public health problems. The advances in next-generation sequencing technologies and powerful computational tools open up new opportunities to explore microbial biosynthetic potential from underexplored sources, with millions of secondary metabolites awaiting discovery. The review highlights challenges associated with discovery of new chemical entities, rich reservoirs provided by untapped taxa, ecological niches or host microbiomes, emerging synthetic biotechnologies to unearth the hidden microbial biosynthetic potential for novel drug discovery at scale and speed. • Large-scale (meta)genomic sequencing of underexplored microbial sources opens up new opportunities for novel NP discovery. • Automated biofoundry workflows are facilitating the refactoring and expression of silent BGCs at scale and speed. • Artificial intelligence has become an important strategy to identify candidate AMPs from complex microbial communities. • The syn-BNP approach opens up new avenues for novel NP discovery in an interdisciplinary and high-throughput manner. [ABSTRACT FROM AUTHOR]

The diversity and secondary metabolite potential of culturable actinomycetes associated with eight different marine sponges collected from the South China Sea and the Yellow sea were investigated. A total of 327 strains were isolated and 108 representative isolates were selected for phylogenetic analysis. Ten families and 13 genera of Actinomycetales were detected, among which five genera represent first records isolated from marine sponges. Oligotrophic medium M5 (water agar) proved to be efficient for selective isolation, and ?Micromonospora-Streptomyces? was proposed as the major distribution group of sponge-associated actinomycetes from the China Seas. Ten isolates are likely to represent novel species. Sponge Hymeniacidon perleve was found to contain the highest genus diversity (seven genera) of actinomycetes. Housekeeping gene phylogenetic analyses of the isolates indicated one ubiquitous Micromonospora species, one unique Streptomyces species and one unique Verrucosispora phylogroup. Of the isolates, 27.5% displayed antimicrobial activity, and 91% contained polyketide synthase and/or nonribosomal peptide synthetase genes, indicating that these isolates had a high potential to produce secondary metabolites. The isolates from sponge Axinella sp. contained the highest presence of both antimicrobial activity and NRPS genes, while those from isolation medium DNBA showed the highest presence of antimicrobial activity and PKS I genes. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Beehives are populated by bacterial species with a protective role against honey bee pathogens thanks to the production of bioactive metabolites. These compounds are largely unexploited despite their high potential interest for pest management. This study evaluated the capability of bacterial species associated with honey bees to produce 2-heptanone, a volatile organic compound with anesthetic properties of the parasitic mite Varroa destructor. The production of this compound was quantified by SPME-GC-MS in a culture filtrate of nine bacterial strains isolated from the surface of honey bees, and the biosynthetic potential was evaluated in bacterial species associated with apiaries by searching for protein homologs putatively involved in its biosynthesis by using biocomputational tools. The findings pointed out that 2-heptanone was produced by Acetobacteraceae bacterium, Bacillus thuringiensis and Apilactobacillus kunkeei isolates in concentrations between 1.5 and 2.6 ng/mL and that its production was strain-specific. Putative methylketone synthase homologs were found in Bacillus, Gilliamella, Acetobacteraceae, Bartonella and Lactobacillaceae, and the protein sequence results were distributed in nine Sequence Similarity Network (SSN) clusters. These preliminary results support the hypothesis that 2-heptanone may act as a mediator of microbial relationships in hives and provide contributions to assess the role and biosynthetic potential of 2-heptanone in apiaries. [ABSTRACT FROM AUTHOR]

The problem of antibiotic resistance has become a challenge for our public health and society; it has allowed infectious diseases to re-emerge as a risk to human health. New antibiotics that are introduced to the market face the rise of resistant pathogens after a certain period of use. The relatively fast development of resistance against some antibiotics seems to be closely linked to their microbial origin and function in nature. Antibiotics in clinical use are merely products of microorganisms or derivatives of microbial products. The evolution of these antimicrobial compounds has progressed with the evolution of the respective resistance mechanisms in microbes for billions of years. Thus, antimicrobial resistance genes are present within the environment and can be taken up by pathogens through horizontal gene transfer. Natural products from bacteria are an important source of leads for drug development, and microbial natural products have contributed the most antibiotics in current clinical use. Bioprospecting for new antibiotics is a labor-intensive task as obstacles such as redetection of known compounds and low compound yields consume significant resources. The number of bacterial isolates one can theoretically investigate for new secondary metabolites is, on the other hand, immense. Therefore, the available capacity for biodiscovery should be focused on the most promising sources for chemical novelty and bioactivity, employing the appropriate scientific tools. This can be done by first looking into under- or unexplored environments for bacterial isolates and by focusing on the promising candidates to reduce the number of subjects. [ABSTRACT FROM AUTHOR]

Actinobacteria that inhabit lichen symbionts are considered a promising yet previously underexplored source of novel compounds. Here, for the first time, we conducted a comprehensive investigation with regard to strain isolation and identification of lichen-associated actinobacteria from Tibet Plateau, antimicrobial activity screening, biosynthetic genes detection, bioactive metabolites identification and activity prediction. A large number of culturable actinomycetes were isolated from lichens around Qinghai Lake, in Qinghai-Tibet Plateau. Twenty-seven strains with distinct morphological characteristics were preliminarily studied. 16S rRNA gene identification showed that 13 strains were new species. The PCR-screening of specific biosynthetic genes indicated that these 27 isolates had abundant intrinsic biosynthetic potential. The antimicrobial activity experiment screened out some potential biological control antagonistic bacteria. The metabolites of 13 strains of Streptomyces with antibacterial activity were analyzed by LC-HRMS, and further 18 compounds were identified by NMR and / or LC-HRMS. The identified compounds were mainly pyrrolidine and indole derivatives, as well as anthracyclines. Seven compounds were identified with less biological activity, then predicted and evaluated their biological activity. The predicted results showed that compound 2 had excellent inhibitory activity on HIV-1 reverse transcriptase. Overall, the results indicate actinobacteria isolated from unexploited plateau lichen are promising sources of biological active metabolite, which could provide important bioactive compounds as potential antibiotic drugs. [ABSTRACT FROM AUTHOR]