Whole-genome sequencing of marine water-derived Curvularia verruculosa KHW-7: a pioneering study.

Marine microorganisms are renowned for being a rich source of new secondary metabolites that are significant to humans. The fungi strain KHW-7 was isolated from the seawater collected from the Gulf of Khambhat, India, and identified as Curvularia verruculosa KHW-7. On a next-generation sequencing platform, C. verruculosa KHW-7's whole-genome sequencing (WGS) and gene annotation were carried out using several bioinformatic methods. The 31.59 MB genome size, 52.3% GC, and 158 bp mean read length were discovered using WGS. This genome also contained 9,745 protein-coding genes, including 852 secreted proteins and 2048 transmembrane proteins. The antiSMASH algorithm used to analyze genomes found 25 secondary metabolite biosynthetic gene clusters (BGCs) that are abundant in terpene, non-ribosomal peptide synthetase (NRPS), and polyketides type 1 (T1PKS). To our knowledge, this is the first whole-genome sequence report of C. verruculosa. The WGS analysis of C. verruculosa KHW-7 indicated that this marine-derived fungus could be an efficient generator of bioactive secondary metabolites and an important industrial enzyme, both of which demand further investigation and development.

Metagenomic analysis of the effects of salinity on microbial community and functional gene diversity in glacial meltwater estuary, Ny-Alesund, Arctic.

Due to the inflow of meltwater from the Midre Lovénbreen glacier upstream of Kongsfjorden, the nutrient concentration of Kongsfjorden change from the estuary to the interior of the fjord. Our objective was to explore the changes in bacterial community structure and metabolism-related genes from the estuary to fjord by metagenomic analysis. Our data indicate that glacial meltwater input has altered the physicochemical properties of the fjords, with a significant effect, in particular, on fjords salinity, thus altering the relative abundance of some specific bacterial groups. In addition, we suggest that the salinity of a fjord is an important factor affecting the abundance of genes associated with the nitrogen and sulfur cycles in the fjord. Changes in salinity may affect the relative abundance of microbial populations that carry metabolic genes, thus affecting the relative abundance of genes associated with the nitrogen and sulfur cycles.

Antibacterial Polyketides Isolated from the Marine-Derived Fungus Fusarium solani 8388.

Seven new polyketides named fusarisolins F-K (1-6) and fusarin I (7) were isolated from the marine-derived fungus Fusarium solani 8388, together with the known anhydrojavanicin (8), 5-deoxybostry coidin (9), and scytalol A (10). Their structures were established by comprehensive spectroscopic data analyses, and by comparison of the 1H and 13C NMR data with those reported in literature. Fusarisolin F (1) contained both a dichlorobenzene group and an ethylene oxide unit, which was rare in nature. In the bioassays, fusarisolin I (4), fusarisolin J (5), and 5-deoxybostry coidin (9) exhibited obvious antibacterial activities against methicillin-resistant Staphylococcus aureus n315 with MIC values of 3, 3, and 6 µg/mL, respectively. Fusarisolin H (3) and fusarisolin J (5) showed inhibitory effects against methicillin-resistant Staphylococcus aureus NCTC 10442 with the same MIC value of 6 µg/mL. With the exception of 5, all other compounds did not show or showed weak cytotoxicities against HeLa, A549, and KB cells; while fusarisolin J (5) demonstrated moderate cytotoxicities against the three human cancer cell lines with CC50 values between 9.21 and 14.02 µM.

A Comprehensive Self-Resistance Gene Database for Natural-Product Discovery with an Application to Marine Bacterial Genome Mining.

In the world of microorganisms, the biosynthesis of natural products in secondary metabolism and the self-resistance of the host always occur together and complement each other. Identifying resistance genes from biosynthetic gene clusters (BGCs) helps us understand the self-defense mechanism and predict the biological activity of natural products synthesized by microorganisms. However, a comprehensive database of resistance genes is still lacking, which hinders natural product annotation studies in large-scale genome mining. In this study, we compiled a resistance gene database (RGDB) by scanning the four available databases: CARD, MIBiG, NCBIAMR, and UniProt. Every resistance gene in the database was annotated with resistance mechanisms and possibly involved chemical compounds, using manual annotation and transformation from the resource databases. The RGDB was applied to analyze resistance genes in 7432 BGCs in 1390 genomes from a marine microbiome project. Our calculation showed that the RGDB successfully identified resistance genes for more than half of the BGCs, suggesting that the database helps prioritize BGCs that produce biologically active natural products.

Identification of the metabolites from co-cultures of marine Streptomyces sp. IMB18-531 and Cladosporium sp. IMB19-099 / 药学学报

A new siderophore chelate (1) and 8 known compounds were identified from the liquid co-cultures of the marine-derived Streptomyces sp. IMB18-531 and Cladosporium sp. IMB19-099 by a combination of chromatography methods, including C18 reversed-phase medium pressure chromatography, gel column chromatography and HPLC. Their structures were determined by spectroscopic analysis and chemical methods as aluminioxamine E (1), desferrioxamine E (2), ferrioxamine E (3), terragine E (4), capsimicin (5), cyclo(L-prolinyl-L-tyrosine) (6), anthranilic acid (7), (Z)-14-methylpentadec-9-enoic acid (8), and (Z)-hexadec-8-enoic acid (9). Compound 2 showed inhibitory activities against the expression of liver fibrosis related genes COL1A1, MMP2, and TIMP2. Compounds 5, 8, and 9 displayed antibacterial activities against methicillin-resistant Staphylococcus aureus, S. epidermidis and Bacillus subtilis, with MICs of 16-64 μg·mL-1. Compound 5 showed cytotoxicities against human pancreatic cancer MIA Paca-2 and human colon cancer HT-29 cell lines with IC50 of 2.9 and 6.3 μmol·L-1, respectively.

Metabolites extracted from microorganisms as potential inhibitors of glycosidases (α-glucosidase and α-amylase): A review.

α-Glucosidase and α-amylase are the two main glycosidases that participate in the metabolism of carbohydrates. Inhibitors of these two enzymes are considered an important medical treatment for carbohydrate uptake disorders, such as diabetes and obesity. Microbes are an important source of constituents that have the potential to inhibit glycosidases and can be used as sources of new drugs and dietary supplements. For example, the α-glucosidase inhibitor acarbose, isolated from Actinoplanes sp., has played an important role in adequately controlling type 2 diabetes, but this class of marketed drugs has many drawbacks, such as poor compliance with treatment and expense. This demonstrates the need for new microorganism-derived resources, as well as novel classes of drugs with better compliance, socioeconomic benefits, and safety. This review introduces the literature on microbial sources of α-glucosidase and α-amylase inhibitors, with a focus on endophytes and marine microorganisms, over the most recent 5 years. This paper also reviews the application of glycosidase inhibitors as drugs and dietary supplements. These studies will contribute to the future development of new microorganism-derived glycosidase inhibitors.

MGCEP 1.0: A Genetic-Engineered Marine-Derived Chassis Cell for a Scaled Heterologous Expression Platform of Microbial Bioactive Metabolites.

Marine microorganisms produce a variety of bioactive secondary metabolites, which represent a significant source of novel antibiotics. Heterologous expression is a valuable tool for discovering marine microbial secondary metabolites; however, marine-derived chassis cell is very scarce. Here, we build an efficient plug-and-play marine-derived gene clusters expression platform 1.0 (MGCEP 1.0) by the systematic engineering of the deep-sea-derived Streptomyces atratus SCSIO ZH16. For a proof of concept, four families of microbial bioactive metabolite biosynthetic gene clusters (BGCs), including alkaloids, aminonucleosides, nonribosomal peptides, and polyketides, were efficiently expressed in this platform. Moreover, 19 compounds, including two new angucycline antibiotics, were produced in MGCEP 1.0. Dynamic patterns of global biosynthetic gene expression in MGCEP 1.0 with or without a heterologous gene cluster were revealed at the transcriptome level. The platform MGCEP 1.0 provides new possibilities for expressing microbial secondary metabolites, especially of marine origin.

Secondary Metabolites from Marine-Derived Bacillus: A Comprehensive Review of Origins, Structures, and Bioactivities.

The marine is a highly complex ecosystem including various microorganisms. Bacillus species is a predominant microbialflora widely distributed in marine ecosystems. This review aims to provide a systematic summary of the newly reported metabolites produced by marine-derived Bacillus species over recent years covering the literature from 2014 to 2021. It describes the structural diversity and biological activities of the reported compounds. Herein, a total of 87 newly reported metabolites are included in this article, among which 49 compounds originated from marine sediments, indicating that marine sediments are majority sources of productive strains of Bacillus species Therefore, marine-derived Bacillus species are a potentially promising source for the discovery of new metabolites.

Cytotoxic Indolocarbazoles From a Marine-Derived Streptomyces Sp. OUCMDZ-5380.

Under the guidance of global natural product social molecular networking, three new indolocarbazoles named streptocarbazoles F-H (1-3), along with staurosporine (4) were isolated from the marine-derived Streptomyces sp. OUCMDZ-5380. Structures of streptocarbazoles F-H were, respectively, determined as N-demethyl-N-hexanoylstaurosporine (1), N-demethyl-N-(2-methyl-3-methoxypyridin-4-yl) staurosporine staurosporine (2), and 4-(N-demethylstaurosporine-N-yl)-1,2-dimethyl-3-methoxypyridinium (3) by spectroscopic analysis and electronic circular dichroism comparison with staurosporine. Compared with staurosporine (4), streptocarbazoles F-H (1-3) showed a selective antiproliferation of the acute myeloid leukemia cell line MV4-11 with the IC50 values of 0.81, 0.55, and 1.88 µM, respectively.

Macrolactin Metabolite Production by Bacillus sp. ZJ318 Isolated from Marine Sediment.

A total of 172 microbial strains were screened and isolated from Arctic Ocean marine sediments at a depth of 42 ~ 3,763 m. A microorganism with strong antibacterial activity against Staphylococcus aureus was identified as Bacillus sp. ZJ318 according to the results of 16S rDNA sequencing and phylogenetic tree analyses. Bioactivity-guided isolation of the new/novel metabolite in the ethyl acetate (EA) extract obtained from the fermentation broth of this strain was followed by chromatographic fractionation and subsequent HPLC purification, leading to the isolation of one known macrolactin. The chemical structure of the macrolactin, which indicated macrolactin J isolation from marine microorganisms for the first time, was assigned based on a high-resolution electrospray ionization mass spectrometer system (HR-EMI-MS), nuclear magnetic resonance (NMR) spectral analyses, and a literature review. To improve macrolactin J production, the corresponding effects of nitrogen sources were investigated, and (NH4)2SO4 was determined to produce the best effect. In addition, the optimal culture conditions were determined by an orthogonal experiment. Under these conditions, the yield of macrolactin J was increased to 2.41 mg/L, which was 2.2 times the original yield. This work lays a foundation for follow-up mechanistic and application research on macrolactin J.

Isolation and Characterization of a Yellow Xanthophyll Pigment-Producing Marine Bacterium, Erythrobacter sp. SDW2 Strain, in Coastal Seawater.

Xanthophylls, a yellow pigment belonging to the carotenoid family, have attracted much attention for industrial applications due to their versatile nature. We report the isolation of a homo xanthophyll pigment-producing marine bacterium, identified as the Erythrobacter sp. SDW2 strain, from coastal seawater. The isolated Erythrobacter sp. SDW2 strain can produce 263 ± 12.9 mg/L (89.7 ± 5.4 mg/g dry cell weight) of yellow xanthophyll pigment from 5 g/L of glucose. Moreover, the xanthophyll pigment produced by the SDW2 strain exhibits remarkable antioxidative activities, confirmed by the DPPH (73.4 ± 1.4%) and ABTS (84.9 ± 0.7%) assays. These results suggest that the yellow xanthophyll pigment-producing Erythrobacter sp. SDW2 strain could be a promising industrial microorganism for producing marine-derived bioactive compounds with potential for foods, cosmetics, and pharmaceuticals.

Optimising the DPPH Assay for Cell-Free Marine Microorganism Supernatants.

Antioxidants prevent ageing and are usually quantified and screened using the 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay. However, this assay cannot be used for salt-containing samples, such as the cell-free supernatants of marine microorganisms that are aggregated under these conditions. Herein, the DPPH solvent (methanol or ethanol) and its water content were optimized to enable the analysis of salt-containing samples, aggregation was observed for alcohol contents of >70%. The water content of methanol influenced the activities of standard antioxidants but did not significantly affect that of the samples. Based on solution stability considerations, 70% aqueous methanol was chosen as the optimal DPPH solvent. The developed method was successfully applied to the cell-free supernatants of marine bacteria (Pseudoalteromonas rubra and Pseudoalteromonas xiamenensis), revealing their high antioxidant activities. Furthermore, it was concluded that this method would be useful for the screening of marine microorganism-derived antioxidants, which also has numerous potential applications, such as salt-fermented foods.

Macrocystis pyrifera Extract Residual as Nutrient Source for the Production of Sophorolipids Compounds by Marine Yeast Rhodotorula rubra.

Seaweed processing generates liquid fraction residual that could be used as a low-cost nutrient source for microbial production of metabolites. The Rhodotorula strain is able to produce antimicrobial compounds known as sophorolipids. Our aim was to evaluate sophorolipid production, with antibacterial activity, by marine Rhodotorula rubra using liquid fraction residual (LFR) from the brown seaweed Macrocystis pyrifera as the nutrient source. LFR having a composition of 32% w/w carbohydrate, 1% w/w lipids, 15% w/w protein and 52% w/w ash. The best culture condition for sophorolipid production was LFR 40% v/v, without yeast extract, artificial seawater 80% v/v at 15 °C by 3 growth days, with the antibacterial activity of 24.4 ± 3.1 % on Escherichia coli and 21.1 ± 3.8 % on Staphylococcus aureus. It was possible to identify mono-acetylated acidic and methyl ester acidic sophorolipid. These compounds possess potential as pathogen controllers for application in the food industry.

Dual α-1,4- and ß-1,4-Glycosidase Activities by the Novel Carbohydrate-Binding Module in α-l-Fucosidase from Vibrio sp. Strain EJY3.

Carbohydrates are structurally and functionally diverse materials including polysaccharides, and marine organisms are known to have many enzymes for the breakdown of complex polysaccharides. Here, we identified an α-l-fucosidase enzyme from the marine bacterium Vibrio sp. strain EJY3 (VejFCD) that has dual α-1,4-glucosidic and ß-1,4-galactosidic specificities. We determined the crystal structure of VejFCD and provided the structural basis underlying the dual α- and ß-glycosidase activities of the enzyme. Unlike other three-domain FCDs, in VejFCD, carbohydrate-binding module-B (CBM-B) with a novel ß-sandwich fold tightly contacts with the CatD/CBM-B main body and provides key residues for the ß-1,4-glycosidase activity of the enzyme. The phylogenetic tree analysis suggests that only a few FCDs from marine microorganisms have the key structural features for dual α-1,4- and ß-1,4-glycosidase activities. This study provides the structural insights into the mechanism underlying the novel glycoside hydrolase activities and could be applied for more efficient utilization in the hydrolysis of complex carbohydrates in biotechnological applications.

Marine microorganisms as an untapped source of bioactive compounds.

The search for novel biologically active molecules has extended to the screening of organisms associated with less explored environments. In this sense, Oceans, which cover nearly the 67% of the globe, are interesting ecosystems characterized by a high biodiversity that is worth being explored. As such, marine microorganisms are highly interesting as promising sources of new bioactive compounds of potential value to humans. Some of these microorganisms are able to survive in extreme marine environments and, as a result, they produce complex molecules with unique biological interesting properties for a wide variety of industrial and biotechnological applications. Thus, different marine microorganisms (fungi, myxomycetes, bacteria, and microalgae) producing compounds with antioxidant, antibacterial, apoptotic, antitumoral and antiviral activities have been already isolated. This review compiles and discusses the discovery of bioactive molecules from marine microorganisms reported from 2018 onwards. Moreover, it highlights the huge potential of marine microorganisms for obtaining highly valuable bioactive compounds.

Isolation of an Extract from the Soft Coral Symbiotic Microorganism Salinispora arenicola Exerting Cytoprotective and Anti-Aging Effects.

Cells have developed a highly integrated system responsible for proteome stability, namely the proteostasis network (PN). As loss of proteostasis is a hallmark of aging and age-related diseases, the activation of PN modules can likely extend healthspan. Here, we present data on the bioactivity of an extract (SA223-S2BM) purified from the strain Salinispora arenicola TM223-S2 that was isolated from the soft coral Scleronephthya lewinsohni; this coral was collected at a depth of 65 m from the mesophotic Red Sea ecosystem EAPC (south Eilat, Israel). Treatment of human cells with SA223-S2BM activated proteostatic modules, decreased oxidative load, and conferred protection against oxidative and genotoxic stress. Furthermore, SA223-S2BM enhanced proteasome and lysosomal-cathepsins activities in Drosophila flies and exhibited skin protective effects as evidenced by effective inhibition of the skin aging-related enzymes, elastase and tyrosinase. We suggest that the SA223-S2BM extract constitutes a likely promising source for prioritizing molecules with anti-aging properties.

Recent progresses in marine microbial-derived antiviral natural products.

Viruses have always been a class of pathogenic microorganisms that threaten the health and safety of human life worldwide. However, for a long time, the treatment of viral infections has been slow to develop, and only a few antiviral drugs have been using clinically. Compared with these from terrestrial environments, marine-derived microorganisms can produce active substances with more novel structures and unique functions. From 2015 to 2019, 89 antiviral compounds of 8 structural classes have been isolated from marine microorganisms, of which 35 exhibit anti-H1N1 activity. This review surveys systematically marine microbial-derived natural products with antiviral activity and illustrates the impact of these compounds on antiviral drug discovery research.

Antitumor Activity of Asperphenin A, a Lipopeptidyl Benzophenone from Marine-Derived Aspergillus sp. Fungus, by Inhibiting Tubulin Polymerization in Colon Cancer Cells.

Marine-derived microorganisms are a valuable source of novel bioactive natural products. Asperphenin A is a lipopeptidyl benzophenone metabolite isolated from large-scale cultivation of marine-derived Aspergillus sp. fungus. The compound has shown potent antiproliferative activity against various cancer cells. However, the underlying mechanism of action remained to be elucidated. In this study, we demonstrated the antitumor activity and molecular mechanism of asperphenin A in human colon cancer cells for the first time. Asperphenin A inhibited the growth of colon cancer cells through G2/M cell cycle arrest followed by apoptosis. We further discovered that asperphenin A can trigger microtubule disassembly. In addition to its effect on cell cycle, asperphenin A-induced reactive oxygen species. The compound suppressed the growth of tumors in a colon cancer xenograft model without any overt toxicity and exhibited a combination effect with irinotecan, a topoisomerase I inhibitor. Moreover, we identified the aryl ketone as a key component in the molecular structure responsible for the biological activity of asperphenin A using its synthetic derivatives. Collectively, this study has revealed the antiproliferative and antitumor mechanism of asperphenin A and suggested its possibility as a chemotherapeutic agent and lead compound with a novel structure.