The PAH degrading microbial consortium was collected from sodic soil of the nursery of Guru Jambheshwar University of Science and Technology, Hisar, Haryana (India). And the soil was artificially amended with phenanthrene and naphthalene to isolate the PAHs degrading microbial consortium. The diversity of microbial consortium was analyzed using the NGS (Next Generation Sequencing) based metagenomic approach. The result of diversity analysis showed species Tepidanaerobacter syntrophicus, Sphingomonas oliophenolica, Arthrobacter psychrochitinipnius, Bifidobacterium bombi, Nocardiodies islandensis, Rhodovibrio sodomensis, Thiorhodococus pfennigii, Aeromicrobium ponti, Steroidobacter dentrificans, Actinomaduria maheshkhaliensis, Dactylosporangium maewongense, Pelotomaculum isophthalicicum, and Nocardioides islandensis were present in the consortium. Moreover, Sphingomonas, Arthrobacter, Sphingobium, Azospirillium, Thirohodococcus, and Pelotomaculum were the prominent pollutant degrader genera in the microbial consortium. Since the bioremediation of these pollutants occurs with a significant reduction in toxicity, the study's perspective is to use this type of consortium for bioremediation of specifically contaminated soil.

Lantipeptides from bacterial sources are increasingly important as biopharmaceuticals because of their broad range of applications. However, the availability of most lantipeptides is low, and systematic approaches for downstream processing of this group of peptides is still lacking. Model-based development for chromatographic separations has proven to be a useful tool for developing reliable purification processes. One important compound of such a model is the adsorption behavior of the components of interest. In ion-exchange chromatography, the adsorption equilibrium between salt and proteins can be described using the steric mass action (SMA) formalism. Beyond, the model parameters may be related to the lanthipeptides physico-chemical properties. In this study, the antiviral lantipeptides labyrinthopeptin A1 and A2, purified from Actinomadura namibiensis culture broth, were characterized for their adsorption behavior in anion-exchange chromatography in the range from pH 5.0-7.4. The experiments necessary to determine the three SMA parameters were chosen in a way to limit the amount of peptides needed. Linear gradient elution was applied successfully to separate A1 and A2 and to determine the characteristic charge νi and the equilibrium constant [Formula: see text] . Batch adsorption experiments using a robotic workstation for high throughput and accuracy provided non-linear adsorption isotherms and the steric factor σi. Labyrinthopeptin A1 and A2 show a very different adsorption behavior even though the fundamental structure of the two peptides is similar. keq of A1 ranging from 0.18 to 0.88 are approximately one order of magnitude smaller than that of A2 ranging from 3.44 to 9.73 indicating the higher affinity of A2 to the stationary phase. At pH 7.0 σ was 1.12 and 0.60 for A1 and A2, respectively which was expected based on the molecular weight of the peptides. The characteristic charge for both peptides was also theoretically estimated from the amino acids involved in electrostatic interactions which was in good agreement with experimental data. Thereby, this work provides an useful approach to estimate SMA parameters based on simple structural information that can be applied early in chromatographic ion-exchange process development for peptides and may help adapting the processes for future designed lanthipeptides.

Bacillus subtilis was applied in peat-based soilless cultivation systems containing a mixed substrate (peat:vermiculite:perlite = 2:1:1, v/v/v) and irrigated by one-strength or four-strength Hoagland's nutrient solution to explore whether it can alleviate inhibition by higher-nutrient solutions (four-strength) and bring benefits to improvements of quality. The results showed that higher-nutrient solutions improved the flavor quality of cucumber fruit; especially, the contents of (E,Z)-2,6-nonadienal and (E)-2-Nonenal were effectively increased, which are the special flavor substances of cucumber. B. subtilis K424 effectively improved growth performance, photosynthetic capacity, vitamin C content, soluble sugars, soluble protein, and total pectin in cucumber under higher nutrition solution conditions. Compared with the higher solution treatment, the bacterial diversity significantly increased, whereas the presence of fungi had no significant difference following the B. subtilis K424 application. Moreover, B. subtilis K424 reduced the relative abundance of Actinomadura and promoted that of the Rhodanobacter, Bacillus, Pseudomonas, Devosiaceae, and Blastobotrys genera. Redundancy analysis showed that Bacillus, Rhodanobacter, and Blastobotrys were positively correlated with the substrate enzyme of sucrase, catalase, and urease. This study provides insight that B. subtilis K424 mitigated the deleterious effects of high levels of nutrition solution on cucumber growth and quality by improving the substrate enzyme, regulating the microbial community structure, and enhancing the photosynthetic capacity.

Endophytic actinobacteria aid in plant development and disease resistance by boosting nutrient uptake or producing secondary metabolites. For the first time, we investigated the culturable endophytic actinobacteria associated with ten epiphytic orchid species of Assam, India. 51 morphologically distinct actinobacteria were recovered from surface sterilized roots and leaves of orchids and characterized based on different PGP and antifungal traits. According to the 16S rRNA gene sequence, these isolates were divided into six families and eight genera, where Streptomyces was most abundant (n=29, 56.86%), followed by Actinomadura, Nocardia, Nocardiopsis, Nocardioides, Pseudonocardia, Microbacterium, and Mycolicibacterium. Regarding PGP characteristics, 25 (49.01%) isolates demonstrated phosphate solubilization in the range of 61.1±4.4 - 289.7±11.9 µg/ml, whereas 27 (52.94%) isolates biosynthesized IAA in the range of 4.0 ± 0.08 - 43.8 ± 0.2 µg/ml, and 35 (68.62%) isolates generated ammonia in the range of 0.9 ± 0.1 - 5.9 ± 0.2 µmol/ml. These isolates also produced extracellular enzymes, viz. protease (43.13%), cellulase (23.52%), pectinase (21.56%), ACC deaminase (27.45%), and chitinase (37.25%). Out of 51 isolates, 27 (52.94%) showed antagonism against at least one test phytopathogen. In molecular screening, most isolates with antifungal and chitinase producing traits revealed the presence of 18 family chitinase genes. Two actinobacterial endophytes, Streptomyces sp. VCLA3 and Streptomyces sp. RVRA7 were ranked as the best strains based on PGP and antifungal activity on bonitur scale. GC-MS examination of ethyl acetate extract of these potent strains displayed antimicrobial compound phenol, 2,4-bis-(1,1-dimethylethyl) as the major metabolite along with other antifungal and plant growth beneficial bioactive chemicals. SEM analysis of fungal pathogen F. oxysporum (MTCC 4633) affected by Streptomyces sp. VCLA3 revealed significant destruction in the spore structure. An in vivo plant growth promotion experiment with VCLA3 and RVRA7 on chili plants exhibited statistically significant (p<0.05) improvements in all of the evaluated vegetative parameters compared to the control. Our research thus gives insight into the diversity, composition, and functional significance of endophytic actinobacteria associated with orchids. This research demonstrates that isolates with multiple plant development and broad-spectrum antifungal properties are beneficial for plant growth. They may provide a viable alternative to chemical fertilizers and pesticides and a sustainable solution for chemical inputs in agriculture.

Atractylodes lancea is an important medicinal plant in traditional Chinese medicine, its rhizome is rich of volatile secondary metabolites with medicinal values and is largely demanded in modern markets. Currently, supply of high-yield, high-quality A. lancea is mainly achieved via cultivation. Certain soil microbes can benefit plant growth, secondary metabolism and induce resistance to environmental stresses. Hence, studies on the effects of soil microbe communities and isolates microorganisms on A. lancea is extremely meaningful for future application of microbes on cultivation. Here we investigated the effects of the inoculation with an entire soil microbial community on the growth, resistance to drought, and accumulation of major medicinal compounds (hinesol, β-eudesmol, atractylon and atractylodin) of A. lancea. We analyzed the interaction between A. lancea and the soil microbes at the phylum and genus levels under drought stress of different severities (inflicted by 0%, 10% and 25% PEG6000 treatments). Our results showed that inoculation with soil microbes promoted the growth, root biomass yield, medicinal compound accumulation, and rendered drought-resistant traits of A. lancea, including relatively high root:shoot ratio and high root water content under drought. Moreover, our results suggested drought stress was more powerful than the selectivity of A. lancea in shaping the root-associated microbial communities; also, the fungal communities had a stronger role than the bacterial communities in protecting A. lancea from drought. Specific microbial clades that might have a role in protecting A. lancea from drought stress were identified: at the genus level, the rhizospheric bacteria Bacillus, Dylla and Actinomadura, and rhizospheric fungi Chaetomium, Acrophialophora, Trichoderma and Thielava, the root endophytic bacteria Burkholderia-Caballeronia-Paraburkholderia, Allorhizobium-Neorhizobium-Pararhizobium-Rhizobium, Dylla and Actinomadura, and the root endophytic fungus Fusarium were closely associated with A. lancea under drought stress. Additionally, we acquired several endophytic Paenibacillus, Paraburkholderia and Fusarium strains and verified they had differential promoting effects on the medicinal compound accumulation in A. lancea root. This study reports the interaction between A. lancea and soil microbe communities under drought stress, and provides insights for improving the outcomes in A. lancea farming via applying microbe inoculation.

Applications of organomineral fertilizer (OMF) are important measures for developing organic agriculture in karst mountain areas. However, the influence of OMF on the structure and function of soil microbial diversity and their relationship with crop yield and quality are still unclear.

Large scale cultivation and chemical investigation of an extract obtained from Actimonadura sp. resulted in the identification of six previously undescribed spirotetronates (pyrrolosporin B and decatromicins C-G; 7-12), along with six known congeners, namely decatromicins A-B (1-2), BE-45722B-D (3-5), and pyrrolosporin A (6). The chemical structures of compounds 1-12 were characterized via comparison with previously reported data and analysis of 1D/2D NMR and MS data. The structures of all new compounds were highly related to the spirotetronate type compounds, decatromicin and pyrrolosporin, with variations in the substituents on the pyrrole and aglycone moieties. All compounds were evaluated for antibacterial activity against the Gram-negative bacteria, Acinetobacter baumannii and Gram-positive bacteria, Staphylococcus aureus and were investigated for their cytotoxicity against the human cancer cell line A549. Of these, decatromicin B (2), BE-45722B (3), and pyrrolosporin B (7) exhibited potent antibacterial activities against both Gram-positive (MIC90 between 1-3 μM) and Gram-negative bacteria (MIC90 values ranging from 12-36 μM) with weak or no cytotoxic activity against A549 cells.

Prodiginines are a large family of microbial secondary metabolites with a core structure of tripyrrole rings. They exhibit not only diverse chemical structures but also rich biological activities, such as anti-cancer, anti-microbial, anti-algae, anti-parasitic, pesticides, and UV radiation resistance. The preferred cytotoxicity to cancer cells rather than normal cells indicates a good biological selectivity and safety, which makes the prodiginines promising candidates for drug development and novel additives for food processing. Until now, 33 prodiginine natural products have been identified in various bacteria, including Serratia, Hahella, Pseudoalteromonas, Vibrio, Zooshikella, Streptomyces, and Actinomadura. However, most efforts are still focused on the star molecule prodigiosin, while little yet is known about other prodiginine members, which retards the research and application of prodiginine compounds. To gain insight into the prodiginine family, we reviewed the recent discoveries on their chemical structures, biosynthesis, biological activities, and mechanisms of action. We believe this article will provide a guideline for new research on prodiginines, such as the discovery of new congeners and drug development. KEY POINTS: • The prodiginines are a large family of natural products with a core structure of tripyrrole rings and exhibit various bioactivities. • The prodiginines have a widespread distribution among many environmental microbes and diverse biosynthetic pathways, indicating important ecological roles and a great potential for new congeners. • The potent biological activities and good selectivity of action make prodiginines good lead compounds for drug development.

Nitrogen (N) is the first essential nutrient for tea growth. However, the effect of soil acidification on soil N cycle and N forms in tea plantation are unclear. In this study, the nitrogen contents, soil enzyme activity and N mineralization rate in acidified soil of tea plantation were measured. Moreover, the effects of soil acidification on N cycling functional genes and functional microorganisms were explored by soil metagenomics. The results showed that the NH4 +-N, available N and net N mineralization rate in the acidified tea soil decreased significantly, while the NO3 --N content increased significantly. The activities of sucrase, protease, catalase and polyphenol oxidase in the acidified tea soil decreased significantly. The abundance of genes related to ammonification, dissimilatory N reduction, nitrification and denitrification pathway in the acidified tea soil increased significantly, but the abundance of functional genes related to glutamate synthesis and assimilatory N reduction pathway were opposite. In addition, the abundance of Proteobacteria, Actinobacteria, Chloroflexi, Nitrospirae, Actinomadura, Nitrospira etc. microorganisms related to nitrification, denitrification and pathogenic effect increased significantly in the acidified tea soil. The correlation results showed that soil pH and N forms were correlated with soil enzyme activity, N cycling function genes and microbial changes. In conclusion, soil acidification results in significant changes in enzyme activity, gene abundance and microorganism involved in various N cycle processes in acidified tea soil, which leads to imbalance of soil N form ratio and is not conducive to N transformation and absorption of tea trees.

The presence of large amounts of antibiotic resistance genes (ARGs) in livestock manures poses an impending, tough safety risk to ecosystems. To investigate more comprehensively the mechanisms of ARGs removal from industrial-scale composting of livestock manure based on biochar addition, we tracked the dynamics of bacterial community and ARGs at various stages of aerobic composting of livestock manures with 10% biochar. There were no significant effects of biochar on the bacterial community and the profiles of ARGs. During aerobic composting, the relative abundance of ARGs and mobile genetic elements (MGEs) showed overall trends of decreasing and then increasing. The key factor driving the dynamics of ARGs was bacterial community composition, and the potential hosts of ARGs were Caldicoprobacter, Tepidimicrobium, Ignatzschineria, Pseudogracilibacillus, Actinomadura, Flavobacterium and Planifilum. The retention of the thermophilic bacteria and the repopulation of the initial bacteria were the dominant reasons for the increase in ARGs at maturation stage. Additionally, among the MGEs, the relative abundance of transposon gene was substantially removed, while the integron genes remained at high relative abundance. Our results highlighted that the suitability of biochar addition to industrial-scale aerobic composting needs to be further explored and that effective measures are needed to prevent the increase of ARGs content on maturation stage.

Nine new hydroxyphenyloxazolines, madurastatin B4, C2, D3 and D4, E1 and E2, F1 as well as G1 and G2 (8-16), along with two new enantiomers of madurastatin D1 (ent-6) and D2 (ent-7) and two known congeners, madurastatin B1 (2) and C1 (5), were isolated from the liquid culture of Actinomadura sp. ST100801 based on the initial activity against Escherichia coli screened in bicarbonate-supplemented Mueller Hinton II medium and identification via molecular networking. Structure elucidation was achieved by comprehensive 1D and 2D NMR as well as MS/MS fragmentation analyses. Their absolute configuration was determined by Marfey's analysis. Complemented with functionalized hydroxyphenyloxazolines (2, 4, 17-18) obtained by total synthesis, the isolated compounds were evaluated for antibacterial activities revealing MICs down to 4 µg ml-1 against Moraxella catarrhalis. Therefore, this study enlarges the family of madurastatin siderophores.

A novel actinomycete strain, named LHW52907T, was isolated from a marine sponge (Leucetta chagosensis) collected in the South China Sea. The strain developed branched mycelia without fragmentation and short spore chains in hook-and- spiral form with wrinkled surfaces, bearing no more 10 spores. The cell-wall hydrolysates contained meso-diaminopimelic acid as the diagnostic diamino acid. The sugars in whole-cell hydrolysates consisted of mannose, ribose, glucose, galactose and madurose. The major fatty acids of the strain were C16 : 0, C17 : 0 and C18 : 1 ω9c. The predominant menaquinone was MK-9(H6). The strain had the highest 16S rRNA gene sequence similarity of 99.72 % to Actinomadura pelletieri DSM 43383T. However, the average nucleotide identity and in silico DNA-DNA hybridization values between them were 93.6 and 52.6 %, respectively, readily distinguishing them as two different species. The results indicate that strain LHW52907T represents a novel species of the genus Actinomadura, for which we propose the name Actinomadura spongiicola sp. nov, with the type strain LHW52907T (=DSM 106571T=CGMCC 4.7596T).

Gut microbiota is involved in maintaining homeostasis, and intestinal dysbiosis may lead to opportunistic infections and diseases. Pathogens can disrupt the gut homeostasis and establish colonization, but how they modulate the microbiome and metabolome along the gut-lung axis warrants further investigation. In the present study, we used a classical low virulence Klebsiella pneumoniae (cKp) strain to address this question. We assessed the gut microbiome and lung metabolome in cKp-infected mice by 16S rRNA sequencing and untargeted liquid chromatography-mass spectrometry, respectively. Our data revealed that cKp infection reduced gut microbiota diversity and altered microbiome composition. Specifically, cKp infection increased the abundance of MWH-CFBk5 and Actinomadura and reduced the abundance of Lachnospiraceae_NK4A136_group, Clostridium sensu_stricto 1, Bifidobacterium, and Intestinimonas at the genus level. Notably, caffeine and caffeine metabolism were significantly affected in the lung by cKp infection. Moreover, Spearman correlation analysis revealed remarkable correlations of specific lung metabolites and bacteria species at the genus level. These findings suggest that cKp infection is linked to gut dysbiosis and alterations in the lung metabolome. This study is of significance for developing innovative gut microbiota-directed therapy for respiratory diseases.

Colorectal cancer (CRC) is a common, and deadly disease. Despite the improved knowledge on CRC heterogeneity and advances in the medical sciences, there is still an urgent need to cope with the challenges and side effects of common treatments for the disease. Natural products (NPs) have always been of interest for the development of new medicines. Actinobacteria are known to be prolific producers of a wide range of bioactive NPs, and scientific evidence highlights their important protective role against CRC. This review is a holistic picture on actinobacter-derived cytotoxic compounds against CRC that provides a good perspective for drug development and design in near future. This review also describes the chemical structure of 232 NPs presenting anti-CRC activity with the being majority of quinones, lactones, alkaloids, peptides, and glycosides. The study reveals that most of these NPs are derived from marine actinobacteria followed by terrestrial and endophytic actinobacteria, respectively. They are predominantly produced by Streptomyces, Micromonospors, Saliniospors and Actinomadura, respectively, in which Streptomyces, as the predominant contributor generating over 76% of compounds exclusively. Besides it provides a valuable snapshot of the chemical structure-activity relationship of compounds, highlighting the presence or absence of some specific atoms and chemical units in the structure of compounds can greatly influence their biological activities. To the best of our knowledge, this is the first comprehensive review on natural actinobacterial compounds affecting different types of CRC. Our study reveals that the high diversity of actinobacterial strains and their NPs derivatives, described here provides a new perspective and direction for the production of new anti-CRC drugs and paves the way to innovation for drugs discovery in the future. The knowledge obtain from this review can help us to understand the pivotal application of actinobacteria in future drugs development.

The mycetoma is a granulomatous chronic disease, subcutaneous disease is the common presentation, very few cases are reported affecting central nervous system, but there are not cases in Renal Transplant (RT).

Mycetoma is a neglected tropical chronic granulomatous inflammatory disease of the skin and subcutaneous tissues. More than 70 species with a broad taxonomic diversity have been implicated as agents of mycetoma. Understanding the full range of causative organisms and their antibiotic sensitivity profiles are essential for the appropriate treatment of infections. The present study focuses on the analysis of full genome sequences and antibiotic inhibitory concentration profiles of actinomycetoma strains from patients seen at the Mycetoma Research Centre in Sudan with a view to developing rapid diagnostic tests. Seventeen pathogenic isolates obtained by surgical biopsies were sequenced using MinION and Illumina methods, and their antibiotic inhibitory concentration profiles determined. The results highlight an unexpected diversity of actinomycetoma causing pathogens, including three Streptomyces isolates assigned to species not previously associated with human actinomycetoma and one new Streptomyces species. Thus, current approaches for clinical and histopathological classification of mycetoma may need to be updated. The standard treatment for actinomycetoma is a combination of sulfamethoxazole/trimethoprim and amoxicillin/clavulanic acid. Most tested isolates had a high IC (inhibitory concentration) to sulfamethoxazole/trimethoprim or to amoxicillin alone. However, the addition of the β-lactamase inhibitor clavulanic acid to amoxicillin increased susceptibility, particularly for Streptomyces somaliensis and Streptomyces sudanensis. Actinomadura madurae isolates appear to have a particularly high IC under laboratory conditions, suggesting that alternative agents, such as amikacin, could be considered for more effective treatment. The results obtained will inform future diagnostic methods for the identification of actinomycetoma and treatment.

A novel actinomycete strain PM05-2T was isolated from the lichen Parmotrema praesorediosum (Nyl.) Hale collected from Chaiyaphum Province, Thailand. The taxonomic position of the strain was studied using the polyphasic approach. Based on the morphology and chemotaxonomic properties, strain PM05-2T was identified as a member of the genus Actinomadura. The whole-cell hydrolysate contained meso-diaminopimelic acid, rhamnose, ribose, xylose, madurose, glucose and galactose. The polar lipids were phosphatidylglycerol, diphosphatidylglycerol, phosphatidylinositol, phosphatidylinositol mannoside, one unidentified phosphoglycolipid, four unidentified phospholipids and one unidentified lipid. The menaquinones were MK-9(H6), MK-9(H4), MK-9(H2), MK-9(H8) and MK-9(H0). The major cellular fatty acids were C16:0 and C18:1 ω9c. Strain PM05-2T showed the highest 16S rRNA gene similarity to Actinomadura hibisca NBRC 15177T (98.58%), Actinomadura kijaniata NBRC 14229T (98.29 %) and Actinomadura namibiensis DSM 44197T (98.14 %). The phylogenetic tree analysis revealed that strain PM05-2T was related to A. hibisca NBRC 15177T, A. kijaniata NBRC 14229T, A. namibiensis DSM 44197T and Actinomadura macrotermitis RB68T. The genomic analysis revealed that average nucleotide identity values based on both blast and MUMmer between strain PM05-2T and the relative type strains ranged from 77.6 to 86.4%. The digital DNA-DNA hybridization values among the strains were lower than the threshold for assigning to the same species. The taxonomic results suggested that strain PM05-2T represented a novel species of the genus Actinomadura for which the name Actinomadura parmotrematis is proposed. The type strain is PM05-2T (=TBRC 15492T=NBRC 115416T).

A total of 37 actinobacteria were isolated from eighteen lichen samples collected in Thailand. Based on the 16S rRNA gene sequences, they were identified into five genera including Actinoplanes (1 strain), Actinomadura (1 strain), Pseudosporangium (1 strain), Wangella (1 strain) and Streptomyces (33 strains). Among these isolates, strain Ptm05T, Ptm01 and Ptm12 showed low 16S rRNA gene similarity and was selected for the further taxonomic study using the polyphasic approach. These strains showed the highest 16S rRNA gene sequence similarity with Streptomyces sparsogenes ATCC 25498T (97.44-97.72%). Strain Ptm05T was selected for the type strain. The chemical cell composition of the strain was similar to the members of Streptomyces genus. LL-diaminopimelic acids were detected in the peptidoglycan. Menaquinones were MK-9(H8) and MK-9(H6). Phosphatidylethanolamine, phosphatidylglycerol, diphosphatidylglycerol, phosphatidylinositol, phosphatidylinositol mannoside, one unidentified phospholipid, one unidentified glycolipid and one unidentified lipid were detected as the polar lipids. The predominant cellular fatty acids are anteiso-C15:0, iso-C15:0, iso-C16:0, iso-C17:0 and C16:0. The dDNA-DNA hybridization values among strain Ptm05T and its closely related Streptomyces type strains were 17.2-18.0%. In addition, the ANIb and ANIm between strain Ptm05T and related Streptomyces type strains were ranged from 75.69 to 76.13% and 85.21 to 85.35%, respectively. Based on phenotypic and genomic evidence, strain Ptm05T (= TBRC 14546T = NBRC 115203T) represents the novel species of the genus Streptomyces for which the name Streptomyces parmotrematis sp. nov. is proposed. This study showed that the lichens are the promising source of the novel actinobacterial taxa.

Mucin-degrading microbes are known to harbor glycosyl hydrolases (GHs) which cleave specific glycan linkages. Although several microbial species have been identified as mucin degraders, there are likely many other members of the healthy gut community with the capacity to degrade mucins. The aim of the present study was to systematically examine the CAZyme mucin-degrading profiles of the human gut microbiota. Within the Verrucomicrobia phylum, all Akkermansia glycaniphila and muciniphila genomes harbored multiple gene copies of mucin-degrading GHs. The only representative of the Lentisphaerae phylum, Victivallales, harbored a GH profile that closely mirrored Akkermansia. In the Actinobacteria phylum, we found several Actinomadura, Actinomyces, Bifidobacterium, Streptacidiphilus and Streptomyces species with mucin-degrading GHs. Within the Bacteroidetes phylum, Alistipes, Alloprevotella, Bacteroides, Fermenitomonas Parabacteroides, Prevotella and Phocaeicola species had mucin degrading GHs. Firmicutes contained Abiotrophia, Blautia, Enterococcus, Paenibacillus, Ruminococcus, Streptococcus, and Viridibacillus species with mucin-degrading GHs. Interestingly, far fewer mucin-degrading GHs were observed in the Proteobacteria phylum and were found in Klebsiella, Mixta, Serratia and Enterobacter species. We confirmed the mucin-degrading capability of 23 representative gut microbes using a chemically defined media lacking glucose supplemented with porcine intestinal mucus. These data greatly expand our knowledge of microbial-mediated mucin degradation within the human gut microbiota.

Fungi colonizing fruits in the field and post-harvest constitute a major threat to the global food sector. This study focuses on the biocontrol of Aspergillus flavus (aflatoxin-producing mold considered carcinogenic by IARC) and Fusarium oxysporum f. sp. albedinis (FOA) (phytopathogenic agent, causal of El Bayoud in the Algerian and Moroccan Sahara). These molds have a significant economic impact and pose a serious human health problem. The aim of this work is to study the antifungal activity of two rare actinomycetes strains; Saccharothrix sp. COL22 and Actinomadura sp. COL08 strains against toxinogenic A. flavus and F. oxysporum f. sp. albedinis. The strains are isolated from Citrullus colocynthis rhizosphere on different media: ISP2, GLM, TSA, Starch-casein-agar and WYE and with different treatments of the samples (physical, chemical treatment and enrichment). The antifungal tests against the pathogenic microorganisms were performed on ISP2, GLM and TSA medium by means of the agar cylinders method. The kinetics of antibiotic production were performed on ISP medium over 16 days. The characterization of the antimicrobial compounds by LC-ESI/MS-MS showed that the bacterial extracts contain Antibiotic SF 2738C, Tetrodecamycin and Aplysillamide B. The phenotypic and molecular studies showed that Saccharothrix sp. COL22 is closely related to the Saccharothrix longispora strain type and that Actinomadura sp. COL08 is closely related to the Actinomadura hibisca strain type. The two strains are rare and showed an interesting activity against toxinogenic A. flavus and F. oxysporum f. sp. albedinis.

Nonheme iron- and α-ketoglutarate (αKG)-dependent halogenases (NHFeHals), which catalyze the regio- and stereoselective halogenation of the unactivated C(sp3)-H bonds, exhibit tremendous potential in the challenging asymmetric halogenation. AdeV from Actinomadura sp. ATCC 39365 is the first identified carrier protein-free NHFeHal that catalyzes the chlorination of nucleotide 2'-deoxyadenosine-5'-monophosphate (2'-dAMP) to afford 2'-chloro-2'-deoxyadenosine-5'-monophosphate. Here, we determined the complex crystal structures of AdeV/FeII/Cl and AdeV/FeII/Cl/αKG at resolutions of 1.76 and 1.74 Å, respectively. AdeV possesses a typical β-sandwich topology with H194, H252, αKG, chloride, and one water molecule coordinating FeII in the active site. Molecular docking, mutagenesis, and biochemical analyses reveal that the hydrophobic interactions and hydrogen bond network between the substrate-binding pocket and the adenine, deoxyribose, and phosphate moieties of 2'-dAMP are essential for substrate recognition. Residues H111, R177, and H192 might play important roles in the second-sphere interactions that control reaction partitioning. This study provides valuable insights into the catalytic selectivity of AdeV and will facilitate the rational engineering of AdeV and other NHFeHals for synthesis of halogenated nucleotides. IMPORTANCE Halogenated nucleotides are a group of important antibiotics and are clinically used as antiviral and anticancer drugs. AdeV is the first carrier protein-independent nonheme iron- and α-ketoglutarate (αKG)-dependent halogenase (NHFeHal) that can selectively halogenate nucleotides and exhibits restricted substrate specificity toward several 2'-dAMP analogues. Here, we determined the complex crystal structures of AdeV/FeII/Cl and AdeV/FeII/Cl/αKG. Molecular docking, mutagenesis, and biochemical analyses provide important insights into the catalytic selectivity of AdeV. This study will facilitate the rational engineering of AdeV and other carrier protein-independent NHFeHals for synthesis of halogenated nucleotides.

In this study, we analyzed if Actinomadura sp. RB99 produces siderophores that that could be responsible for the antimicrobial activity observed in co-cultivation studies. Dereplication of high-resolution tandem mass spectrometry (HRMS/MS) and global natural product social molecular networking platform (GNPS) analysis of fungus-bacterium co-cultures resulted in the identification of five madurastatin derivatives (A1, A2, E1, F, and G1), of which were four new derivatives. Chemical structures were unambiguously confirmed by HR-ESI-MS, 1D and 2D NMR experiments, as well as MS/MS data and their absolute structures were elucidated based on Marfey's analysis, DP4+ probability calculation and total synthesis. Structure analysis revealed that madurastatin E1 (2) contained a rare 4-imidazolidinone cyclic moiety and madurastatin A1 (5) was characterized as a Ga3+ -complex. The function of madurastatins as siderophores was evaluated using the fungal pathogen Cryptococcus neoformans as model organism. Based on homology models, we identified the putative NRPS-based gene cluster region of the siderophores in Actinomadura sp. RB99.

Background Mycetoma is widespread in Yemen; however, there are only a few documented reports on the entity from this geographical area. Methods A prospective study of 184 cases of mycetoma (male 145 and female 39) from different regions of north-western Yemen was conducted between July 2000 and May 2014. Clinical profile was recorded in a standardized protocol. The diagnosis was based on clinical features, X-ray studies, examination of grains, and histopathology. Results Eumycetoma was diagnosed in 129, caused by Madurella mycetomatis in 124, Leptosphaeria senegalensis in one and pale grain fungus in four, whereas actinomycetoma occurred in 55, caused by Streptomyces somaliensis in 29, Actinomadura madurai in nine, Actinomadura pelletieri in one, and Nocardia in sixteen. Eumycetoma cases were treated with prolonged course of antifungal drugs, mostly ketoconazole, with itraconazole being used in four patients, along with excision or debulking. Results were better when antifungal drugs were given two to three months before surgery and in those who received itraconazole. Actinomycetoma cases were initially treated with co-trimoxazole monotherapy; later streptomycin was added in 30 cases. Six patients who did not show adequate improvement and two others from the start were treated with modified Welsh regimen and with good results. Limitations Identification of different causative agents was done by histopathology and could not be reconfirmed by culture. Conclusion Mycetoma is widespread in north-western Yemen with a higher incidence of eumycetoma and a majority of the cases were caused by Madurella mycetomatis. Modified Welsh regimen in actinomycetoma and itraconazole with excision in eumycetoma showed the best results.

Baseline assessments of marine microbial studies are very limited around ecologically sensitive areas of the Nuclear Power Plant (NPP) site with respect to their occurrence, distribution, role in adaptation, and their potential remediation process. The distribution and diversity of marine microbes are largely dependent on the physicochemical parameters relating to a specific area, especially spore-producing marine actinobacteria are a source for indigenous bioremediation agents. Marine actinobacterial diversity with conventional and 16 S rRNA gene analysis was done with different pre-treatment conditions and selective media. Totally, 170 different strains are identified in genera level and it belongs to 18 genera with dominant by Streptomyces sp. (75species) followed by Nocardiposis sp, (18species) Rhodococcus sp. (14species). Multiple k-dominance plots simplified the perception of marine actinobacteria according to genera level influence to standard stock. This is the first kind of study in India and the results could act as baseline inventory in terms of microbial diversity around NPP sites. Further, a potential strain of Actinomadura sp. (T5S13) produced 243.7 mg/L of EPS and remediate the Uranium radionuclides. The functional group shifting and adsorption nature were also confirmed by SEM with EDS analysis.

Chemical investigation of the fermentation products of a deep sea water-derived actinomycete, Actinomadura sp. KD439, identified seven new angucyclinones, designated as kumemicinones A-G (1-7), together with the known SF2315B and miaosporone E. NMR and MS spectroscopic analyses, combined with X-ray crystallography and quantum chemical calculations of NMR chemical shifts and electronic circular dichroism (ECD) spectra, uncovered the structures of new angucyclinones as regioisomers of SF2315B at the allyl alcohol unit (1 and 2), an epoxy ring-opened γ-hydroxy enone isomer (3), a B/C-ring-rearranged product (4), or dimers with a new mode of bridging (5-7), adding new structural variation to this antibiotic group. The absolute configuration of SF2315B was also determined by comparison of ECD spectra with those of 1 and 2. All the angucyclinones exhibited cytotoxicity against P388 murine leukemia cells, with IC50 values ranging from 1.8 to 53 μM.

This study investigated effects of composite microbes (CMs) (Phanerochaete chrysosporium and Trichoderma longibrachiatum) on humification during co-composting of biogas residue, spent mushroom substrate and rice straw. Results showed that CMs inoculation elevated degradation ratios of cellulose, hemicellulose and lignin by 7.86%, 8.87% and 6.45%, and contents of humus and humic acid were correspondingly promoted by 15.5% and 23.6%, respectively. Relative abundances of bacteria associated with refractory macromolecules degradation (Flavobacterium, Anseongella and Actinomadura) and cellulolytic fungi (Hypocreales_Incertae_sedis, Hypocreaceae and Psathyrellaceae) were raised by CMs addition. Redundancy analysis demonstrated a positive correlation between microbial communities and temperature, fulvic acid and lignocellulose contents. Moreover, CMs inoculation promoted pathways of xenobiotics biodegradation and metabolism, and biosynthesis of other secondary metabolites, which was closely associated with lignocellulose degradation and humus formation. These results suggested that biological inoculation could enhance composting efficiency and improve compost quality, benefiting biogas residues composting.

The Ojo de Liebre Lagoon is a Marine Protected Area that lies within a UNESCO World Heritage Site and is a critical habitat for important migratory species such as the grey whale and bird species. Unique hypersaline environments, such as the Ojo de Liebre Lagoon, are underexplored in terms of their bacterial and chemical diversity, representing a potential source for new bioactive compounds with pharmacological properties. Actinobacteria are one of the most diverse and prolific taxonomic bacterial groups in terms of marine bioactive compounds. This study aimed to identify the culturable actinobacterial community inhabiting the Lagoon, as well as to test their potential as new sources of anticancer compounds with pharmacological potential. A selective isolation approach focused on spore-forming bacteria from 40 sediment samples generated a culture collection of 64 strains. The 16S rRNA gene analyses identified three phyla in this study, the Actinobacteria, Firmicutes and Proteobacteria, where the phylum Actinobacteria dominated (57%) the microbial community profiles. Within the Actinobacteria, nine different genera were isolated including the Actinomadura, Micromonospora, Nocardiopsis, Plantactinospora and Streptomyces sp. We observed seasonal differences on actinobacteria recovery. For instance, Micromonospora strains were recovered during the four sampling seasons, while Arthrobacter and Pseudokineococcus were only isolated in February 2018, and Blastococcus, Rhodococcus and Streptomyces were uniquely isolated in June 2018. Ethyl acetate crude extracts derived from actinobacterial cultures were generated and screened for cytotoxic activity against six cancer cell lines. Strains showed promising low percentages of viability on lung (H1299), cervical (SiHa), colon (Caco-2) and liver (HepG2) cancer lines. Molecular networking results suggest many of the metabolites produced by these strains are unknown and they might harbour novel chemistry. Our results showed the Ojo de Liebre Lagoon is a novel source for isolating diverse marine actinobacteria which produce promising bioactive compounds for potential biotechnological use as anticancer agents.

The Estremadura Spur pockmarks are a unique and unexplored ecosystem located in the North Atlantic, off the coast of Portugal. A total of 85 marine-derived actinomycetes were isolated and cultured from sediments collected from this ecosystem at a depth of 200 to 350 m. Nine genera, Streptomyces, Micromonospora, Saccharopolyspora, Actinomadura, Actinopolymorpha, Nocardiopsis, Saccharomonospora, Stackebrandtia, and Verrucosispora were identified by 16S rRNA gene sequencing analyses, from which the first two were the most predominant. Non-targeted LC-MS/MS, in combination with molecular networking, revealed high metabolite diversity, including several known metabolites, such as surugamide, antimycin, etamycin, physostigmine, desferrioxamine, ikarugamycin, piericidine, and rakicidin derivatives, as well as numerous unidentified metabolites. Taxonomy was the strongest parameter influencing the metabolite production, highlighting the different biosynthetic potentials of phylogenetically related actinomycetes; the majority of the chemical classes can be used as chemotaxonomic markers, as the metabolite distribution was mostly genera-specific. The EtOAc extracts of the actinomycete isolates demonstrated antimicrobial and antioxidant activity. Altogether, this study demonstrates that the Estremadura Spur is a source of actinomycetes with potential applications for biotechnology. It highlights the importance of investigating actinomycetes from unique ecosystems, such as pockmarks, as the metabolite production reflects their adaptation to this habitat.

Earthworms and their casts have been widely used for organic waste degradation and plant growth promotion. The microbial communities that reside in the guts and casts of earthworms markedly influence both applications. In the present study, next-generation sequencing was applied to identify the microbial communities in the guts and casts of three epigeic earthworm species, Eudrilus eugeniae, Perionyx excavatus, and Eisenia fetida, reared under two different feeding conditions. A total of 580 genera belonging to 43 phyla were identified. By comparing bacterial diversity among samples divided into groups based on the earthworm species, sample types, and conditions, the beta diversity analysis supported the impact of the sample type and suggested that there was significant dissimilarity of the bacterial diversity between the gut and cast. Besides, bacterial Phylum compositions within the group were compared. The result showed that the top three high relative frequency phyla found in the casts were the same regardless of earthworm species, while those found in the gut depended on both the condition and earthworm species. Focusing on the cellulolytic and plant growth-promoting bacteria, certain cellulolytic bacteria, Paenibacillus, Comamonas, and Cytophaga, were found only in the cast. Citrobacter and Streptomyces aculeolatus were detected only in the guts of earthworms reared in the bedding containing vegetables and bedding alone, respectively. Besides, Actinomadura and Burkholderia were detected only in the gut of E. eugeniae and E. fetida, respectively. The results proved that the microbial composition was affected by sample type, condition, and earthworm species. In addition, the proportion of these beneficial bacteria was also influenced by these factors. Hence, the information from this study can be used as a guide for selecting earthworm species or their casts for more efficient organic waste decomposition and plant growth promotion.