Streptomyces Research Articles

Synthesis and Cytotoxicity of Cyclic Octapeptide Surugamides with Varied N-Acyl Moieties.

Surugamides are a group of non-ribosomal peptides produced by Streptomyces spp. Several derivatives possess acyl groups, which are proposed to be attached to a lysine side chain after backbone-macrocyclization during biosynthesis. To date, five different acyl groups have been identified in nature, yet their impacts on biological activity remain underexplored. Here we synthesized surugamide B derivatives with varied acyl moieties. Biological evaluations revealed that larger hydrophobic acyl groups on lysine ε-NH2 enhance cytotoxicity.

Urdamycin V from Streptomyces sp induces p53 independent apoptosis in cervical cancer cells inconsiderate of HPV status and inhibited growth of gram-positive human pathogens

In cervical cancer, loss of p53 or mutant non-functional p53 and hyperactivated mTOR/Akt pathway positively correlates to cancer progression. Urdamycin V isolated from Streptomyces OA293 is a recently isolated novel angucycline derivative that in the present study showcased induction of p53 independent apoptosis in both HPV (Human papillomavirus) positive and negative cervical cancer cell lines. Apoptosis induction was via phosphorylation modulation in the cell growth regulating proteins along mTORC2/Akt/p38/Erk pathway. The compound was also tested against human pathogens and selectively inhibited gram-positive strains, Streptococcus pyogenes and Staphylococcus aureus. The present study put forward urdamycins as a potential therapeutic that places promise for further research.

Biosynthesis of Atypical Angucyclines Unveils New Ring Rearrangement Reactions Catalyzed by Flavoprotein Monooxygenases.

Six new angucycline structures, including spirocyclione A (1), which contains an unusual oxaspiro[5.5]undecane architecture, and its ring-A-cleaved product spirocyclione B (2), were discovered by heterologous expression of a type II polyketide biosynthetic gene cluster captured from a marine actinomycete strain Streptomyces sp. HDN155000. Three flavoprotein monooxygenases are confirmed to be responsible for the oxidative carbon skeleton rearrangements in the biosynthesis of compounds 1 and 2. The obtained compounds showed promising cytotoxicity against different types of cancer cells.

Isolation and antifungal activity assessment of natural compounds from the culture medium of actinobacterium Streptomyces sp. BC129-2

Two previously undescribed compounds, including one phenylpropanoid derivative, BC129–2 (1) and one p-menthane analogue, cis-p-menthane-7,8-diol (2), were isolated from the EtOAc-soluble fraction of the culture broth of an actinomycete Streptomyces sp. BC129–2. The structures of all isolates were elucidated on the basis of extensive analyses of spectroscopic data and comparison with literature data. Their antifungal activity was also evaluated. Our results showed that 2 constituents (compounds 1 &2) possessed mild antifungal activity against Fusarium sp. LC8, Neopestalotiopsis sp. BCRC 35002, and Colletotrichum gloeosporioides BCRC 35178. It is worth mentioning that the chemical composition of the type strain Streptomyces sp. BC129–2 has never been studied.

Analysis of the Immunomodulator Profile of Secondary Metabolites Derived from Streptomyces sp.

Analysis of the Immunomodulator Profile of Secondary Metabolites Derived from Streptomyces sp.

Biological Activity of Streptomyces sp. Isolated from Soil in the Municipality of Pinheiro-MA

Biological Activity of Streptomyces sp. Isolated from Soil in the Municipality of Pinheiro-MA

Optimization of anti-MRSA compound production by Streptomyces sp. AR05 using an integrated RSM-ANN-GA approach

Optimization of anti-MRSA compound production by Streptomyces sp. AR05 using an integrated RSM-ANN-GA approach

Mining of thermophilic biosurfactant producers for solid-state fermentation

Solid-state fermentation (SSF) is an emerging technology for organic waste valorisation to marketable bio products. SSF scale-up is hindered by heat transfer problems that could be diminished operating under thermophilic conditions. Compost samples collected from food waste composting facility in a primary school in Barcelona and textile industry sample from Faisalabad Pakistan were subjected to isolation of thermophilic biosurfactant producing microorganisms. Altogether 43 isolates were screened through biosurfactant qualitative screening, but 18 isolates dominated with promising results which were further shortlisted under solid-state culture to select the five significant performers belonging to Bacillus sp., Aspergillus sp., and Streptomyces sp. The performance of the five isolates in SSF was assessed in time course studies in 0.5-L packed bed bioreactor using winterization oil cake (WOC), wheat bran and glucose as substrates combined with wheat straw as support material. All five isolates colonized the substrate well in SSF systems and exhibited considerable glucose consumption and adaptation within the SSF setup. The fermentation extracts indicated promising surface-active properties as observed by emulsification and oil displacement analysis. These findings provide an effective enrichment strategy for screening of thermophilic biosurfactant producers and can aid establishment of the scale up for the enhanced metabolite production.

Atroposelective Synthesis of Axial Biaryls by Dynamic Kinetic Resolution Using Engineered Imine Reductases

AbstractAxially chiral biaryl compounds are ubiquitous scaffolds in natural products, bioactive molecules, chiral ligands and catalysts, but biocatalytic methods for their asymmetric synthesis are limited. Herein, we report a highly efficient biocatalytic route for the atroposelective synthesis of biaryls by dynamic kinetic resolution (DKR). This DKR approach features a transient six‐membered aza‐acetal‐bridge‐promoted racemization followed by an imine reductase (IRED)‐catalyzed stereoselective reduction to construct the axial chirality under ambient conditions. Directed evolution of an IRED from Streptomyces sp. GF3546 provided a variant (S‐IRED‐Ss‐M11) capable of catalyzing the DKR process to access a variety of biaryl aminoalcohols in high yields and excellent enantioselectivities (up to 98 % yield and >99 : 1 enantiomeric ratio). Molecular dynamics simulation studies on the S‐IRED‐Ss‐M11 variant revealed the origin of its improved activity and atroposelectivity. By exploiting the substrate promiscuity of IREDs and the power of directed evolution, our work further extends the biocatalysts’ toolbox to construct challenging axially chiral molecules.

Heterologous expression of lasso peptides with apparent participation in the morphological development in Streptomyces

Lasso peptides, ribosomally synthesized and post-translationally modified peptides, are primarily produced by bacteria and some archaea. Streptomyces lasso peptides have been known for their antimicrobial, anticancer, and antiviral properties. However, understanding their role in the morphology and production of secondary metabolites remains limited. We identified a previously unknown lasso peptide gene cluster in the genome of Streptomyces sp. L06. This gene cluster (LASS) produces two distinct lasso peptides, morphosin-1 and − 2. Notably, morphosin-2 is a member of a new subfamily of lasso peptides, with BGCs exhibiting a similar structure. When LASS was expressed in different Streptomyces hosts, it led to exciting phenotypic changes, including the absence of spores and damage in aerial mycelium development. In one of the hosts, LASS even triggered antibiotic formation. These findings open up a world of possibilities, suggesting the potential role of morphosins in shaping Streptomyces’ morphological and biochemical development.

Antimicrobial potential of Streptomyces sp. NP73 isolated from the forest soil of Northeast India against multi-drug resistant Escherichia coli.

This study reports the isolation and characterization of a Streptomyces sp. from soil, capable of producing bioactive secondary metabolites active against a variety of bacterial human pathogens. We targeted the antimicrobial activity against Escherichia coli ATCC-BAA 2469, a clinically relevant strain of bacteria harbouring resistance genes for carbapenems, extended spectrum beta-lactams, tetracyclines, fluoroquinones, etc. Preliminary screening using the spot inoculation technique identified Streptomyces sp. NP73 as the potent strain among the 74 isolated Actinomycetia strain. 16S rRNA gene and whole genome sequencing (WGS) confirmed its taxonomical identity and helped in the construction of the phylogenetic tree. WGS revealed the predicted pathways and biosynthetic gene clusters responsible for producing various types of antibiotics including the isolated compound. Bioactivity guided fractionation and chemical characterization of the active fraction, carried out using liquid chromatography, gas chromatography-mass spectrometry, infra-red spectroscopy, and nuclear magnetic resonance spectroscopy, led to the tentative identification of the active compound as Pyrrolo[1,2-a] pyrazine-1,4-dione, hexahydro-, a diketopiperazine molecule. This compound exhibited excellent antimicrobial and anti-biofilm properties against E. coli ATCC-BAA 2469 with an MIC value of 15.64µg ml-1, and the low cytotoxicity of the compound identified in this study provides hope for future drug development.

Bioconversion of agriculture by-products with functionally enhanced Streptomyces sp. SCUT-3: Fish skin as a model

With the global population continuously rising, efficient bioconversion of inedible agricultural by-products is crucial for human food and energy sustainability. We here propose solid-state fermentation approaches to efficiently convert biopolymers into oligomers/monomers by accelerating the natural degradation process of the versatile Streptomyces sp. strain SCUT-3. Using fish skin as a representative by-product, 54.3 g amino acids and 14.7 g peptides (91 % < 2500 Da) were recovered from 89.0 g protein in 100 g tilapia skin sample by collagenase-overexpressed SCUT-3 for seven days at a 1:4 substrate:liquid ratio. Fish skin collagen hydrolysates exhibited excellent anti-oxidation, anti-hypertension, scratch-repairing, anti-aging, anti-ultraviolet radiation, and anti-inflammation effects on human skin fibroblasts In vitro and zebrafish larvae in vivo, indicating their potential applications in healthcare/skincare and anti-atopic dermatitis. As Laozi said, the divine law follows nature. This study underscores the efficacy of genetically engineered SCUT-3 according to its natural biomass utilization laws in large-scale biopolymer conversion.

One Undescribed Sesquiterpene from Streptomyces sp.

One Undescribed Sesquiterpene from Streptomyces sp.

Genome Mining for Diazo-Synthesis-Related Genes in Streptomyces sp. CS057 Unveiled the Cryptic Biosynthetic Gene Cluster crx for the Novel 3,4-AHBA-Derived Compound Crexazone 2.

Natural products play a crucial role in drug development, addressing the escalating microbial resistance to antibiotics and the treatment of emerging diseases. Progress in genome sequencing techniques, coupled with the development of bioinformatics tools and the exploration of uncharted habitats, has highlighted the biosynthetic potential of actinomycetes. By in silico screening for diazo-related gene genomes from twelve Streptomyces strains isolated from Attini leaf-cutting ants, the new crx biosynthetic gene cluster (BGC) was identified in Streptomyces sp. CS057. This cluster, highly conserved in several Streptomyces strains, contains genes related to diazo group formation and genes for the biosynthesis of 3,4-AHBA. By overexpressing the LuxR-like regulatory gene crxR1, we were able to activate the crx cluster, which encodes the biosynthesis of three 3,4-AHBA-derived compounds that we named crexazones (CRXs). The chemical structure of crexazones (CRXs) was determined by LC-DAD-HRMS-based dereplication and NMR spectroscopic analyses and was found to correspond to two known compounds, 3-acetamido-4-hydroxybenzoic acid (CRX1) and the phenoxazinone texazone (CRX3), and a novel 3,4-AHBA-containing compound herein designated as CRX2. Experimental proof linking the crx BGC to their encoded compounds was achieved by generating mutants in selected crx genes.

Toxicokinetics, in vivo metabolic profiling and tissue distribution of chlorfenapyr in mice.

Chlorfenapyr is a novel broad-spectrum insecticide derived from natural pyrrole derivatives produced by Streptomyces spp. It acts as a pro-insecticide and is metabolically converted to the active metabolite, tralopyril. Chlorfenapyr poisoning is known for its delayed neurological symptoms and high mortality. Unfortunately, information on the toxicokinetics, metabolism and tissue distribution of chlorfenapyr and tralopyril is still lacking. In this study, the metabolic profile, toxicokinetics and tissue distribution of chlorfenapyr and tralopyril after oral administration at a toxic dose in mice were investigated. Twenty metabolites were identified in plasma, urine and feces, which were mainly formed by dealkylation, oxidative dechlorination and reductive dechlorination. Toxicokinetic results showed that chlorfenapyr was rapidly converted to tralopyril after administration, and the in vivo half-life (t1/2), area under the curve (AUC) and peak concentration (Cmax) values of tralopyril were significantly higher than those of chlorfenapyr (P < 0.05). Tissue distribution experiments confirmed that the metabolite tralopyril had a longer half-life, a lower clearance and a wide distribution in different organs and tissues compared to chlorfenapyr. It was also able to cross the blood-brain barrier, suggesting a potential association with brain lesions. In addition, a sensitive and rapid LC-MS/MS analytical method was established for the detection of chlorfenapyr and tralopyril. In conclusion, this study provided valuable metabolic, toxicokinetic and tissue distribution information, contributing to future risk assessment and forensic identification in cases of chlorfenapyr poisoning. We recommend considering the assessment of tralopyril levels, which may be of greater therapeutic importance in the management of chlorfenapyr poisoning.

Characterization of Antibiotic Actinomycin D Isolated from Streptomyces parvulus Collected from Marine Sponge of Barrang Lompo Island, Makassar, Indonesia.

Microorganisms associated with sea sponges have proven to be good natural product resources that are biologically active and pharmaceutically important. This research aimed to identify actinomycetes related to a sponge from Bar-ranglompo Island Makassar and the antibacterial compounds. Identification of actinomycetes was based on molecular characterization of sequence gen16S rRNA. The antibacterial compound was separated using vacuum liquid chromatog-raphy and preparative Thin Layer Chromatography (TLC). The structure determination was done based on spectroscopy 1H-NMR, 13C-NMR, 2D NMR, and mass spectra. Molecular characterization showed that actinomycetes strain BLP 20 had the closest relationship with Streptomyces parvulus and Uncultured Streptomyces sp. with a similarity value of 83%. The results obtained from the characterization of antibacterial compounds based on spectroscopic data indicate that these compounds lead to Actinomycin D. Characterization and identification of Strain 20 / BLP by molecular phylogenetic analysis of 16S rRNA sequences revealed the closest relationship with Uncultured Streptomy-ces sp and S. parvulus with a similarity value of 83 %, which indicated a new species. The structure of the active compound isolated from actinomycetes strain 20 / BLP leads to Actino-mycin D.

Unveiling the potential of bacterial isolates from plastic-polluted environments: enhancement of polyhydroxybutyrate biodegradation

This study explores the biodegradation potential of microbial isolates focusing on their ability to utilize biopolymers as sole carbon source. Previously described isolates have been investigated through agar-based screen for the ability to degrade plastic-related substrates in powder form, and four strains have been selected for further assessment. Polyhydroxybutyrate (PHB) films degradation was examined through liquid culture, soil burial, and respirometry assays. Structural and chemical alterations in PHB were analysed using scanning electron microscopy (SEM), Fourier-transform infrared spectroscopy (FTIR), and differential scanning calorimetry (DSC). The most successful strains were tested for the ability to degrade PHB/bacterial nanocellulose (BNC) blends. Bacillus sp. DG90 excelled in PHB degradation, achieving 60% weight loss in liquid culture, while Streptomyces sp. DG19 exhibited a notable degradation rate of 51 ± 1.7%. Soil burial assays underscored the impact of environmental factors on degradation rates, emphasizing the role of soil composition and nitrogen availability. In respirometry assay, PHB films were severely defragmented by Streptomyces sp. DG19 with overall weight loss of 83%, while for Bacillus sp. DG90, this percentage reached 39%. FTIR and DSC analyses suggested potential hydrolysis and structural alterations in treated samples. This study observed rapid PHB degradation (83% in 3 weeks) while, considering the complex composition of modern biomaterials, also showcased the potential of examined strains to degrade PHB-BNC blends up to 85%.

Genome Mining and Genetic Manipulation Reveal New Isofuranonaphthoquinones in Nocardia Species.

The identification of specialized metabolites isolated from microorganisms is urgently needed to determine their roles in treating cancer and controlling multidrug-resistant pathogens. Naphthoquinones act as anticancer agents in various types of cancers, but some toxicity indicators have been limited in their appropriate application. In this context, new isofuranonaphthoquinones (ifnq) that are less toxic to humans could be promising lead compounds for developing anticancer drugs. The aim of this study is to identify and characterize novel furanonaphthoquinones (fnqs) from Nocardia sp. CS682 and to evaluate their potential therapeutic applications. Analysis of the genome of Nocardia sp. CS682 revealed the presence of a furanonaphthoquinone (fnq) gene cluster, which displays a similar genetic organization and high nucleotide sequence identity to the ifnq gene cluster from Streptomyces sp. RI-77, a producer of the naphthoquinones JBIR-76 and JBIR-77. In this study, the overexpression of the Streptomyces antibiotic regulatory protein (SARP) in Nocardia sp. CS682DR (nargenicin gene-deleted mutant) explicitly produced new fnqs, namely, NOC-IBR1 and NOC-IBR2. Subsequently, the role of the SARP regulator was confirmed by gene inactivation using CRISPR-Cas9 and complementation studies. Furthermore, antioxidant, antimicrobial, and cytotoxicity assays were performed for the isolated compounds, and it was found that NOC-IBR2 exhibited superior activities to NOC-IBR1. In addition, a flexible methyltransferase substrate, ThnM3, was found to be involved in terminal methylation of NOC-IBR1, which was confirmed by in vitro enzyme assays. Thus, this study supports the importance of genome mining and genome editing approaches for exploring new specialized metabolites in a rare actinomycete called Nocardia.

Integrated genomic and functional analysis of Streptomyces sp. UP1A-1 for bacterial wilt control and solanaceae yield increase

Ralstonia solanacearum is one of the most destructive soil-borne pathogen, causing bacterial wilt to the solanaceae vegetables. Streptomyces sp. UP1A-1 isolated from healthy solanaceae rhizosphere soil, exhibited the lowest disease incidence and increased fruit yield of solanaceae vegetables. However, the genomic and functional properties of UP1A-1 are unclear. Therefore, we conducted the present study to elucidate the genomic characteristics of UP1A-1 by whole genome sequencing. The results indicate that the genome of Streptomyces sp. UP1A-1 consists of 8,252,902 bp and contains 72.42 % G + C. We identified the genes that confer plant growth promoting (PGP) function, which include those involved in siderophore production, indole-3-acetic acid biosynthesis, phosphate solubilization, nitrogen metabolism, and potassium metabolism. We also identified several other genes, such as chitinase, peroxidase, superoxide dismutase, catalase, proline biosynthesis, and glucose dehydrogenase, which are believed to be involved in the control of wilt disease. These genes revealed that the strain UP1A-1 has physiologically adapted to varied environmental conditions and could potentially control both abiotic and biotic stresses.

Identification, fermentation optimization, and biocontrol efficacy of actinomycete YG-5 for the prevention of Alternaria leaf spot disease in star anise

Star anise (Illicium verum), a valuable spice tree, faces significant threats from fungal diseases, particularly Alternaria leaf spot. This study investigates the potential of a soil-derived actinomycete strain, YG-5, as a biocontrol agent against Alternaria tenuissima, the causative pathogen on Alternaria leaf spot in star anise. Through comprehensive morphology, physiology, biochemistry, and genetic analyses, we identified the isolate as Streptomyces sp. YG-5. The strain exhibited broad-spectrum antimicrobial activity against several plant pathogens, with inhibition rates ranging between 36.47 to 80.34%. We systematically optimized the fermentation conditions for YG-5, including medium composition and cultivation parameters. The optimized process resulted in an 89.56% inhibition rate against A. tenuissima, a 14.72% improvement over non-optimized conditions. Notably, the antimicrobial compounds produced by YG-5 demonstrated stability across various temperatures, pH levels, and UV irradiation. In vivo efficacy trials showed promising results, with YG-5 fermentation broth reducing Alternaria leaf spot incidence on star anise leaves by 56.95%. These findings suggest that Streptomyces sp. YG-5 holds significant potential as a biocontrol agent against Alternaria leaf spot in star anise cultivation, offering a sustainable approach to disease management in this valuable crop.