Search Results (55)

Marine-derived Actinomycetota have emerged as promising sources of bioactive natural products, particularly filamentous actinomycetes (e.g., Streptomyces). However, members from non-filamentous genera have showed potential biotechnological importance. In this study, we performed a comprehensive genomic characterization of two bioactive Brevibacterium strains, Brevibacterium luteolum (B. luteolum) 26C and Brevibacterium casei (B. casei) 13A, isolated from two Red Sea sponges. Whole-genome sequencing and taxonomic analysis confirmed species-level identification, marking the first documented report of these species within the Red Sea ecosystem. The two strains displayed antimicrobial activity against Staphylococcus aureus, Escherichia coli, and Candida albicans. Additionally, functional annotation revealed multiple genomic islands (GIs) enriched with genes conferring heavy metal resistance, DNA repair enzymes, nutrient acquisition, and mobile genetic elements, highlighting potential evolutionary adaptations to the harsh physicochemical conditions of the Red Sea. Genome mining identified biosynthetic gene clusters, including those encoding ε-poly-L-lysine, tropodithietic acid, ectoine, and carotenoids. The comparative analysis of orthologous gene clusters from both strains and their counterparts from terrestrial ecosystems highlighted potential marine adaptive genetic mechanisms. This study highlights the biosynthetic potential of B. luteolum 26C and B. casei 13A and their ecological role as active competitors and potential defensive associates within the sponge microbiome. Full article

Background/Objectives: Despite the continuous development of medicine, the treatment of dermatological fungal infections is difficult due to their chronic nature, recurrence, and resistance of some pathogens to standard therapies. In order to improve the effectiveness of treatment, not only are new active substances with antifungal activity synthesized, but new, unconventional carriers are also developed for substances already used. Methods: Therefore, the focus of this research was to evaluate the possibility of using a combination of two cross-linking techniques for sodium alginate ionic cross-linking with Zn²⁺ ions and electrostatic interaction with ε-poly-L-lysine. The pharmaceutical properties, antifungal activity against Candida strains, and compatibility with human fibroblasts of the designed hydrogels were assessed. Results: It was shown that the double cross-linking process increased the viscosity of the developed hydrogels, improved bioadhesive properties to hairless mice skin, and provided an extended release profile of the active substance. In addition, obtained formulations were characterized by improved antifungal effect against C. albicans, C. krusei, and C. parapsilosis. Prepared hydrogels expressed biocompatibility with human fibroblasts. Conclusions: Dual-cross-linked alginate hydrogels are a promising dermatological formulation that might improve the efficacy of posaconazole in the treatment of antifungal infections. Full article

Epsilon-poly-l-lysine (ε-PL) is a potent antimicrobial agent, but strategies to enhance its biosynthesis remain limited due to insufficient understanding of its physiological regulation. This study explores the interaction between Streptomyces albulus and heterogeneous microbial extracts, with a focus on actinomycete-derived signals. The S. gilvosporeus extract induces the highest ε-PL production (3.4 g/L), exceeding the control by 2.6-fold and outperforming B. cinerea by 1.8-fold. Multi-omics analyses combined with morphological and biochemical profiling reveal that the induced state is characterized by intensified central carbon flux, enhanced lipid turnover, elevated respiratory activity, and cofactor regeneration, alongside suppression of competing secondary pathways. Morphological alterations, including denser mycelial aggregation and compact colony structures, accompany these metabolic shifts. Compared to B. cinerea, S. gilvosporeus elicits more pronounced stress adaptation and metabolic reprogramming in S. albulus. These findings suggest that interspecies interactions can activate intrinsic aggression resistance mechanisms, thereby driving ε-PL biosynthesis through a previously unrecognized physiological route. Full article

This study aimed to investigate the efficacy of a composite coating composed of 150 mg/L ε-Poly-L-lysine (ε-PL) and 5 g/L chitosan (CTS) in extending the shelf life and maintaining the postharvest quality of fresh Tremella fuciformis. Freshly harvested T. fuciformis were treated by surface spraying, with distilled water serving as the control. The effects of the coating on storage quality, physicochemical properties, reactive oxygen species (ROS) metabolism, and membrane lipid metabolism were evaluated during storage at (25 ± 1) °C. The results showed that the ε-PL/CTS composite coating significantly retarded quality deterioration, as evidenced by reduced weight loss, maintained whiteness and color, and higher retention of soluble sugars, soluble solids, and soluble proteins. The coating also effectively limited water migration and loss. Mechanistically, the coated T. fuciformis exhibited enhanced antioxidant capacity, characterized by increased superoxide anion (O₂⁻) resistance capacity, higher activities of antioxidant enzymes (SOD, CAT, APX), and elevated levels of non-enzymatic antioxidants (AsA, GSH). This led to a significant reduction in malondialdehyde (MDA) accumulation, alongside improved DPPH radical scavenging activity and reducing power. Furthermore, the ε-PL/CTS coating preserved cell membrane integrity by inhibiting the activities of lipid-degrading enzymes (lipase, LOX, PLD), maintaining higher levels of key phospholipids (phosphatidylinositol and phosphatidylcholine), delaying phosphatidic acid accumulation, and consequently reducing cell membrane permeability. In conclusion, the ε-PL/CTS composite coating effectively extends the shelf life and maintains the quality of postharvest T. fuciformis by modulating ROS metabolism and preserving membrane lipid homeostasis. This study provides a theoretical basis and a practical approach for the quality control of fresh T. fuciformis. Full article

Network polymers with β-cyclodextrin moieties were prepared by nucleophilic substitution reactions between polyamines, linear polyethyleneimine (LPEI), polyallylamine (PAA), (ε-poly-L-lysine) (EPL), and monochlorotriazinyl-β-cyclodextrin (MCTCD) in methanol/water mixed solvent or water. The reactions under conditions of high material concentration (30 wt%) and a feed ratio of [MCT]/[NH] = 0.5 (mol/mol) successfully yield porous polymers via reaction-induced phase separation. The molecular structure of the polyamines and reaction conditions strongly affected the morphology of the resulting porous polymers. The porous polymers were composed of connected particles, gathered (slightly connected) particles, and/or disordered bulky structures, with sizes of 10⁻⁹ m–10⁻⁸ m. An increase in the molecular weight of LPEI and PAA and the feed molar ratio of [MCT]/[NH] tended to decrease the particle size. Young’s moduli of the LPEI-MCTCD and PAA-MCTCD porous polymers increased with an increase in bulk density, which was derived from small particle sizes. The wide particle size distribution and disordered structure caused collapse by the compression under 50 N of pressure. An LPEI-MCTCD adsorbed methyl orange, methylene blue, and phenolphthalein through ionic interactions, π–π interaction, and/or β-cyclodextrin inclusion. Full article

Guava fruit is susceptible to decay, leading to losses in storability and quality. ε-Poly-l-lysine (ε-PL) is a safe antimicrobial polypeptide that has proven to be effective in preserving produce’s quality. In the present research, ε-PL, at multiple concentrations (1, 2 and 4 g/L), was adopted to treat guavas, and the fruit were stored at 25 °C for 15 d. The results indicated that ε-PL retarded the guava storability decline and enhanced its quality. Treated guavas had a better appearance, as well as the lower disease index, relative electrolytic leakage, weight loss, respiration intensity, a* and b* values and reducing sugar content. They also showed higher firmness, commercially acceptable fruit rate, titratable acidity, L* value, total soluble sugar, vitamin C and sucrose levels. The optimal concentration of ε-PL was determined to be 2 g/L. Furthermore, compared to control guavas, fruit treated with 2 g/L ε-PL exhibited lower levels of superoxide anion, hydrogen peroxide and malondialdehyde but higher antioxidant enzyme activities in terms of ascorbate peroxidase, peroxidase, catalase and superoxide dismutase. These findings suggested that ε-PL raised the antioxidant enzyme activities to enhance the fruit’s antioxidant ability. This, in turn, reduced the reactive oxygen species levels and lipid peroxidation, ultimately improving the guava’s quality. Consequently, ε-PL is of practical significance for commercial application as it suppresses decay and stabilizes the quality of guavas, enhancing their postharvest marketability. Full article

ε-poly-l-lysine (ε-PL), a natural food preservative, has garnered widespread attention. It is mainly produced by Streptomyces albulus, but the production by wild-type strains fails to meet the demands of industrialization. To address this issue, adaptive laboratory evolution (ALE) was successfully employed in this study, subjecting S. albulus CICC 11022 to environmental stresses such as acidic pH and antibiotics (rifampicin, gentamicin, and streptomycin). As a result of ALE, an evolutionary strain S. albulus C214 was obtained, exhibiting an increase in ε-PL production and cell growth by 153.23% and 234.51%, respectively, as compared with the original strain. Genomic and metabolic analyses revealed that mutations occurred in genes responsible for transcriptional regulation, transporter, cell envelope, energy metabolism, and secondary metabolite synthesis, as well as the enrichment of metabolites involved in the biosynthesis of ε-PL. These findings hold great significance for elucidating the mechanism underlying ε-PL synthesis. Full article

ε-Poly-L-lysine (ε-PL) is a natural preservative that has excellent properties such as high safety, good antibacterial effect, wide antibacterial spectrum, and high temperature resistance compared to other food preservatives. At present, the main production strain of ε-PL is Streptomyces albulus (S. albulus). Due to the large amount of mycelium and by-products during fermentation, its production cost is much higher than other food preservatives, which seriously hinders the application of ε-PL in the food industry. Corynebacterium glutamicum (C. glutamicum) is a food safety strain that is widely used in the fermentation industry to produce various amino acids. Its ability to produce high amounts of L-lysine can provide sufficient precursor substances for the synthesis of ε-PL, making it an ideal strain for the heterologous expression of ε-PL synthase genes (pls). In this experiment, a recombinant C. glutamicum capable of synthesizing ε-PL and exhibiting certain physiological resistance to ε-PL was obtained by amplifying pls and heterologous expression in C. glutamicum for the first time. Further optimization of the fermentation temperature, initial pH, and inoculation amount of the recombinant strain resulted in an increase in the ε-PL fermentation yield from 0.12 g/L to 0.22 g/L. Finally, through adaptive evolution of the recombinant strain, the ε-PL tolerance of the recombinant strain was increased to 1.3 g/L, and the yield of ε-PL ultimately reached 0.34 g/L, which increased by 54.55% compared to the initial strain. The recombinant C. glutamicum constructed in this study can significantly shorten the fermentation cycle, reduce bacterial volume and the synthesis of secondary metabolites, which is beneficial for the separation and purification of products, thereby further reducing the production cost of ε-PL and accelerating the process of replacing chemical food preservatives with natural food preservatives. Full article

Hydrogels have emerged as promising biomaterials due to their excellent performance; however, their biocompatibility, biodegradability, and absorbability still require improvement to support a broader range of medical applications. This paper presents a new biofunctionalized hydrogel based on in situ crosslinking between maleimide-terminated four-arm-poly(ethylene glycol) (4–arm–PEG–Mal) and poly(ε-lysine) (ε–PL). The PEG/ε–PL hydrogels, named LG–n, were rapidly formed via amine/maleimide reaction by mixing 4–arm–PEG–Mal and ε–PL under physiological conditions. The corresponding dry gels (DLG–n) were obtained through a freeze-drying technique. ¹H NMR, FT–IR, and SEM were utilized to confirm the structures of 4–arm–PEG–Mal and LG–n (or DLG–n), and the effects of solid content on the physicochemical properties of the hydrogels were investigated. Although high solid content could increase the swelling ratio, all LG–n samples exhibited a low equilibrium swelling ratio of less than 30%. LG–7, which contained moderate solid content, exhibited optimal compression properties characterized by a compressive fracture strength of 45.2 kPa and a deformation of 69.5%. Compression cycle tests revealed that LG–n demonstrated good anti-fatigue performance. In vitro degradation studies confirmed the biodegradability of LG–n, with the degradation rate primarily governing the drug (ceftibuten) release efficiency, leading to a sustained release duration of four weeks. Cytotoxicity tests, cell survival morphology observation, live/dead assays, and hemolysis tests indicated that LG–n exhibited excellent cytocompatibility and low hemolysis rates (<5%). Furthermore, the broad-spectrum antibacterial activity of LG–n was verified by an inhibition zone method. In conclusion, the developed LG–n hydrogels hold promising applications in the medical field, particularly as drug sustained-release carriers and wound dressings. Full article

Among the known breast cancers, the subtype with HER2 receptors-overexpressing cells is associated with a poor prognosis. The adopted monoclonal antibody Trastuzumab has improved clinical outcomes, but it is associated with drug resistance and relatively high costs. The present work adopted the peptide solid-phase synthesis method to synthesise branched poly(ε-lysine) peptide dendrons with 8 branching arms integrating, at their carboxy terminal molecular root, either an arginine or the HER2 receptor-binding sequence LSYCCK or the scramble sequence CSCLYK. These dendrons were synthesised in quantities higher than 100 mg/batch and with a purity exceeding 95%. When tested with two types of breast cancer cells, the dendrons led to levels of inhibition in the HER2 receptor-overexpressing breast cancer cells (SKBR3) comparable to Trastuzumab and higher than breast cancer cells with low receptor expression (MDA-MB-231) where inhibition was more moderate. Noticeably, the presence of the amino acid sequence LSYCCK at the dendron molecular root did not appear to produce any additional inhibitory effect. This was demonstrated also when the scramble sequence CSCLYK was integrated into the dendron and by the lack of any antiproliferative effect by the control linear target sequence. The specific inhibitory effect on proliferation was finally proven by the absence of cytotoxicity and normal expression of the cell migration marker N-Cadherin. Therefore, the present study shows the potential of poly(ε-lysine) dendrons as a cost-effective alternative to Trastuzumab in the treatment of HER2-positive breast cancer. Full article

Self-healing, stretchable, and moldable hydrogels have a great potential application in tissue engineering and soft robotics. Despite great success in reported hydrogels, it is still a great challenge to construct the moldable hydrogels with an ultrafast self-healing performance. Herein, the composite hydrogels (PBLH) with ultrafast self-healing, stretchable, and moldable properties were successfully constructed by poly (vinyl alcohol) (PVA), borate (B), ε-poly-l-lysine (EPL), and hyaluronic acid (HA) based on an efficient one-pot method. Fourier transform infrared spectroscopy, X-ray diffraction, and rheological measurements confirmed the formation of a dynamic network among PVA, B, EPL, and HA through the cross-linking of dynamic borate bonds, electrostatic interaction, and hydrogen bonding. Having fabricated the dynamic network structure, the damage gap of the composite hydrogels can heal within 1 min, presenting an excellent self-healing ability. Simultaneously, the composite hydrogels can be molded into various shapes, and the length of the composite hydrogels can be stretched to 15 times their original length. In addition, the composite hydrogels exhibited an excellent antibacterial property against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli). Our results illustrated that the composite hydrogels not only retain the advantages of traditional hydrogels but also possess ultrafast self-healing, outstanding stretchable and antibacterial properties, presenting a prospective candidate for constructing biomedical materials. Full article

Polyamide-6 (PA) is a popular textile polymer having desirable mechanical and thermal properties, chemical stability, and biocompatibility. However, PA nanofibers are prone to bacterial growth and user discomfort. ε-Poly-L-lysine (PL) is non-toxic, antimicrobial, and hydrophilic but lacks spinnability due to its low molecular weight. Given its similar backbone structure to PA, with an additional amino side chain, PL was integrated with PA to develop multifunctional nanofibers. This study explores a simple, scalable method by which to obtain PL nanofibers by utilizing the structurally similar PA as the base. The goal was to enhance the functionality of PA by addressing its drawbacks. The study demonstrates spinnability of varying concentrations of PL with base PA while exploring compositions with higher PL concentrations than previously reported. Electrospinning parameters were studied to optimize the nanofiber properties. The effects of PL addition on morphology, hydrophilicity, thermal stability, mechanical performance, and long-term antimicrobial activity of nanofibers were evaluated. The maximum spinnable concentration of PL in PA-based nanofibers resulted in super hydrophilicity (0° static water contact angle within 10 s), increased tensile strength (1.02 MPa from 0.36 MPa of control), and efficient antimicrobial properties with long-term stability. These enhanced characteristics hold promise for the composite nanofiber’s application in medical and protective textiles. Full article

Safe and eco-friendly preservatives are crucial to preventing food spoilage and illnesses, as foodborne diseases caused by pathogens result in approximately 600 million cases of illness and 420,000 deaths annually. ε-Poly-L-lysine (ε-PL) is a novel food preservative widely used in many countries. However, its commercial application has been hindered by high costs and low production. In this study, ε-PL’s biosynthetic capacity was enhanced in Streptomyces albulus WG608 through metabolic engineering guided by multi-omics techniques. Based on transcriptome and metabolome data, differentially expressed genes (fold change >2 or <0.5; p < 0.05) and differentially expressed metabolites (fold change >1.2 or <0.8) were separately subjected to gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. The integrative analysis of transcriptome, metabolome, and overexpression revealed the essential roles of isocitrate lyase, succinate dehydrogenase, flavoprotein subunit, diaminopimelate dehydrogenase, polyphosphate kinase, and polyP:AMP phosphotransferase in ε-PL biosynthesis. Subsequently, a strain with enhanced ATP supply, L-lysine supply, and ε-PL synthetase expression was constructed to improve its production. Finally, the resulting strain, S. albulus WME10, achieved an ε-PL production rate of 77.16 g/L in a 5 L bioreactor, which is the highest reported ε-PL production to date. These results suggest that the integrative analysis of the transcriptome and metabolome can facilitate the identification of key pathways and genetic elements affecting ε-PL synthesis, guiding further metabolic engineering and thus significantly enhancing ε-PL production. The method presented in this study could be applicable to other valuable natural antibacterial agents. Full article

Gray mold, caused by Botrytis cinerea, poses significant threats to various crops, while it can be remarkably inhibited by ε-poly-L-lysine (ε-PL). A previous study found that B. cinerea extracts could stimulate the ε-PL biosynthesis of Streptomyces albulus, while it is unclear whether the impact of the B. cinerea signal on ε-PL biosynthesis is direct or indirect. This study evaluated the role of elevated reactive oxygen species (ROS) in efficient ε-PL biosynthesis after B. cinerea induction, and its underlying mechanism was disclosed with a transcriptome analysis. The microbial call from B. cinerea could arouse ROS elevation in cells, which fall in a proper level that positively influenced the ε-PL biosynthesis. A systematic transcriptional analysis revealed that this proper dose of intracellular ROS could induce a global transcriptional promotion on key pathways in ε-PL biosynthesis, including the embden-meyerhof-parnas pathway, the pentose phosphate pathway, the tricarboxylic acid cycle, the diaminopimelic acid pathway, ε-PL accumulation, cell respiration, and energy synthesis, in which sigma factor HrdD and the transcriptional regulators of TcrA, TetR, FurA, and MerR might be involved. In addition, the intracellular ROS elevation also resulted in a global modification of secondary metabolite biosynthesis, highlighting the secondary signaling role of intracellular ROS in ε-PL production. This work disclosed the transcriptional mechanism of efficient ε-PL production that resulted from an intracellular ROS elevation after B. cinerea elicitors’ induction, which was of great significance in industrial ε-PL production as well as the biocontrol of gray mold disease. Full article

In this study, we designed the association of the organoselenium compound 5′-Seleno-(phenyl)-3′-(ferulic-amido)-thymidine (AFAT-Se), a promising innovative nucleoside analogue, with the antitumor drug paclitaxel, in poly(ε-caprolactone) (PCL)-based nanoparticles (NPs). The nanoprecipitation method was used, adding the lysine-based surfactant, 77KS, as a pH-responsive adjuvant. The physicochemical properties presented by the proposed NPs were consistent with expectations. The co-nanoencapsulation of the bioactive compounds maintained the antioxidant activity of the association and evidenced greater antiproliferative activity in the resistant/MDR tumor cell line NCI/ADR-RES, both in the monolayer/two-dimensional (2D) and in the spheroid/three-dimensional (3D) assays. Hemocompatibility studies indicated the safety of the nanoformulation, corroborating the ability to spare non-tumor 3T3 cells and human mononuclear cells of peripheral blood (PBMCs) from cytotoxic effects, indicating its selectivity for the cancerous cells. Furthermore, the synergistic antiproliferative effect was found for both the association of free compounds and the co-encapsulated formulation. These findings highlight the antitumor potential of combining these bioactives, and the proposed nanoformulation as a potentially safe and effective strategy to overcome multidrug resistance in cancer therapy. Full article