Producers Of Natural Products Research Articles

Expression of Syo_1.56 SARP Regulator Unveils Potent Elasnin Derivatives with Antibacterial Activity.

Actinomycetes are prolific producers of natural products, particularly antibiotics. However, a significant proportion of its biosynthetic gene clusters (BGCs) remain silent under typical laboratory conditions. This limits the effectiveness of conventional isolation methods for the discovery of novel natural products. Genetic interventions targeting the activation of silent gene clusters are necessary to address this challenge. Streptomyces antibiotic regulatory proteins (SARPs) act as cluster-specific activators and can be used to target silent BGCs for the discovery of new antibiotics. In this study, the expression of a previously uncharacterized SARP protein, Syo_1.56, in Streptomyces sp. RK18-A0406 significantly enhanced the production of known antimycins and led to the discovery of 12 elasnins (1-12), 10 of which were novel. The absolute stereochemistry of elasnin A1 was assigned for the first time to be 6S. Unexpectedly, Syo_1.56 seems to function as a pleiotropic rather than cluster-specific SARP regulator, with the capability of co-regulating two distinct biosynthetic pathways, simultaneously. All isolated elasnins were active against wild-type and methicillin-resistant Staphylococcus aureus with IC50 values of 0.5-20 μg/mL, some of which (elasnins A1, B2, and C1 and proelasnins A1, and C1) demonstrated moderate to strong antimalarial activities against Plasmodium falciparum 3D7. Elasnins A1, B3, and C1 also showed in vitro inhibition of the metallo-β-lactamase responsible for the development of highly antibiotic-resistant bacterial strains.

Advancing Natural Product Discovery: A Structure-Oriented Fractions Screening Platform for Compound Annotation and Isolation.

Natural product discovery is hindered by the lack of tools that integrate untargeted nuclear magnetic resonance and mass spectrometry data on a library scale. This article describes the first application of the innovative NMR/MS-based machine learning tool, the "Structure-Oriented Fractions Screening Platform (SFSP)", enabling functional-group-guided fractionation and accelerating the discovery and characterization of undescribed natural products. The concept was applied to the extract of a marine fungus known to be a prolific producer of diverse natural products. With the assistance of SFSP, we isolated 24 flavipidin derivatives and five phenalenone analogues from Aspergillus sp. GE2-6, revealing 27 undescribed compounds. Compounds 7-22 were proposed as isomeric derivatives featuring a 5/6-ring fusion, formed by the dimerization of flavipidin E (5). Compounds 23 and 24 were envisaged as isomeric derivatives with a 6/5/6-ring fusion, generated through the degradation of two flavipidin E molecules. Furthermore, flavipidin A (1) and asperphenalenone E (28) exhibited potent anti-influenza (PR8) activities, with IC50 values of 21.9 ± 0.2 and 12.9 ± 0.1 μM, respectively. Meanwhile, asperphenalenone (26) and asperphenalenone P (27) treatments exhibited significant inhibition of HIV pseudovirus infection in 293FT cells, boasting IC50 values of 6.1 ± 0.9 and 4.6 ± 1.1 μM, respectively. Overall, SFSP streamlines natural product isolation through NMR and MS data integration, as showcased by the discovery of numerous undescribed flavipidins and phenalenones based on NMR olefinic signals and low-field hydroxy signals.

Penicillium janthinellum: A Potential Producer of Natural Products

Penicillium is a kind of common filamentous fungi yielding high levels of secondary metabolites with diverse structures and attractive activities. Among these fungi, Penicillium janthinellum is a potential producer of secondary metabolites whose natural products have been noticed due to their various chemical structures and biological activities. This review summarizes the sources, distribution, bioactivities and structural characteristics of compounds isolated from P. janthinellum from 1980 to 2023. A total of 153 natural products have been isolated from P. janthinellum, of which 65 were new compounds. The compounds separated from P. janthinellum exhibit diverse skeletal chemical structures, concentrated in the categories of polyketides (40%), alkaloids (31%) and terpenoids (14%). P. janthinellum-derived compounds display attractive biological activities, such as cytotoxic, antibacterial, antifungal and antiviral activities. These results indicate that P. janthinellum is a potential fungus for producing bioactive secondary metabolites which can be used as precursors for new drugs.

Challenging old microbiological treasures for natural compound biosynthesis capacity.

Strain collections are a treasure chest of numerous valuable and taxonomically validated bioresources. The Leibniz Institute DSMZ is one of the largest and most diverse microbial strain collections worldwide, with a long tradition of actinomycetes research. Actinomycetes, especially the genus Streptomyces, are renowned as prolific producers of antibiotics and many other bioactive natural products. In light of this, five Streptomyces strains, DSM 40971T, DSM 40484T, DSM 40713T, DSM 40976T, and DSM 40907T, which had been deposited a long time ago without comprehensive characterization, were the subject of polyphasic taxonomic studies and genome mining for natural compounds based on in vitro and in silico analyses. Phenotypic, genetic, and phylogenomic studies distinguished the strains from their closely related neighbors. The digital DNA-DNA hybridization and average nucleotide identity values between the five strains and their close, validly named species were below the threshold of 70% and 95%-96%, respectively, determined for prokaryotic species demarcation. Therefore, the five strains merit being considered as novel Streptomyces species, for which the names Streptomyces kutzneri sp. nov., Streptomyces stackebrandtii sp. nov., Streptomyces zähneri sp. nov., Streptomyces winkii sp. nov., and Streptomyces kroppenstedtii sp. nov. are proposed. Bioinformatics analysis of the genome sequences of the five strains revealed their genetic potential for the production of secondary metabolites, which helped identify the natural compounds cinerubin B from strain DSM 40484T and the phosphonate antibiotic phosphonoalamide from strain DSM 40907T and highlighted strain DSM 40976T as a candidate for regulator-guided gene cluster activation due to the abundance of numerous "Streptomyces antibiotic regulatory protein" (SARP) genes.

The Genus Cladosporium: A Prospective Producer of Natural Products.

Cladosporium, a genus of ascomycete fungi in the Dematiaceae family, is primarily recognized as a widespread environmental saprotrophic fungus or plant endophyte. Further research has shown that the genus is distributed in various environments, particularly in marine ecosystems, such as coral reefs, mangroves and the polar region. Cladosporium, especially the marine-derived Cladosporium, is a highly resourceful group of fungi whose natural products have garnered attention due to their diverse chemical structures and biological activities, as well as their potential as sources of novel leads to compounds for drug production. This review covers the sources, distribution, bioactivities, biosynthesis and structural characteristics of compounds isolated from Cladosporium in the period between January 2000 and December 2022, and conducts a comparative analysis of the Cladosporium isolated compounds derived from marine and terrestrial sources. Our results reveal that 34% of Cladosporium-derived natural products are reported for the first time. And 71.79% of the first reported compounds were isolated from marine-derived Cladosporium. Cladosporium-derived compounds exhibit diverse skeletal chemical structures, concentrating in the categories of polyketides (48.47%), alkaloids (19.21%), steroids and terpenoids (17.03%). Over half of the natural products isolated from Cladosporium have been found to have various biological activities, including cytotoxic, antibacterial, antiviral, antifungal and enzyme-inhibitory activities. These findings testify to the tremendous potential of Cladosporium, especially the marine-derived Cladosporium, to yield novel bioactive natural products, providing a structural foundation for the development of new drugs.

Biosynthetic mechanism of the yellow pigments in the marine bacterium Pseudoalteromonas sp. strain T1lg65.

The Pseudoalteromonas genus marine bacteria have attracted increasing interest because of their abilities to produce bioactive metabolites. The pigmented Pseudoalteromonas group encodes more secondary metabolite biosynthetic gene clusters (BGCs) than the non-pigmented group. Here, we report a yellow pigmented bacterium Pseudoalteromonas sp. strain T1lg65, which was isolated from a mangrove forest sediment. We showed that the yellow pigments of T1lg65 belong to the group of lipopeptide alterochromides. Further genetic analyses of the alterochromide BGC revealed that the yellow pigments are biosynthesized by aryl-polyene synthases and nonribosomal peptide synthases. Within the gene cluster, altA encodes a tyrosine ammonia acid lyase, which catalyzes synthesis of the precursor 4-hydroxycinnamic acid (4-HCA) from tyrosine in the alterochromide biosynthetic pathway. In addition, altN, encoding a putative flavin-dependent halogenase, was proven to be responsible for the bromination of alterochromides based on gene deletion, molecular docking, and site mutagenesis analyses. In summary, the biosynthetic pathway, precursor synthesis, and bromination mechanism of the lipopeptide alterochromides were studied in-depth. Our results expand the knowledge on biosynthesis of Pseudoalteromonas pigments and could promote the development of active pigments in the future.IMPORTANCEThe marine bacteria Pseudoalteromonas spp. are important biological resources because they are producers of bioactive natural products, including antibiotics, pigments, enzymes, and antimicrobial peptides. One group of the microbial pigments, alterochromides, holds a great value for their novel lipopeptide structures and antimicrobial activities. Previous studies were limited to the structural characterization of alterochromides and genome mining for the alterochromide biosynthesis. This work focused on the biosynthetic mechanism for alterochromide production, especially revealing functions of two key genes within the gene cluster for the alterochromide biosynthesis. On the one hand, our study provides a target for metabolic engineering of the alterochromide biosynthesis; on the other hand, the 4-HCA synthase AltA and brominase AltN show potential in the biocatalyst industry.

Draft Genome Sequencing of Microcoleus sp. HI-ES Isolated from Freshwater in Iraq: Cyanobacterial Strain

Background: Cyanobacteria are a widely dominated group of microorganisms in nature that produce a diverse range of metabolites. Whilst the enormous number of bacterial genomes has deposited in the public databases, the number of cyanobacterial genomes remains limited. Aims: This study aimed to sequence the whole genome of an Iraqi cyanobacterium isolate, designed as Microcoleus sp. HI-ES. Methods: Microcoleus sp. HI-ES was isolated from a freshwater sample collected from the Mosul Dam lake. GB-11 liquid medium was used for primary isolation whereas agarose-GB-11 medium supplemented with lysozyme (100 µg/ml), imipenem (100 µg/ml), streptomycin (100 µg/ml), and cycloheximide (20 µg/ml) was used to obtain an axenic Microcoleus sp. HI-ES culture. Specialized bioinformatics tools were used for genome assembly, annotation, whole genome-based taxonomy analysis, in silico whole genome DNA-DNA hybridization (isDDH), and biosynthetic gene clusters (BGCs) detection. Results: The results showed that Microcoleus sp. HI-ES genome consists of 4,671,230 bp with a GC content of 47.7% distributed within 6417 contigs and a total of 6264 coding sequences. The whole genome-based phylogeny and isDDH values showed that Microcoleus sp. HI-ES is closed to the type strains: Microcoleus asticus IPMA8, Microcoleus vaginatus PCC 9802, M. vaginatus FGP-2, and Oscillatoria nigroviridis PCC 7112 with isDDH values of 61.7%, 59.8%, 59.8%, and 54.5%, respectively. Ten secondary metabolite BGCs were predicted in Microcoleus sp. HI-ES including four nonrobosomal peptides (NRPs) such as one NRPs, two resorcinol, two terpenes, and one T1PKS. The draft genome sequence of Microcoleus sp. HI-ES has been deposited at DDBJ/ENA/GenBank under the accession number JAPTMT000000000. Conclusion: The contribution of the depositing of the whole genome sequencing of Microcoleus sp. HI-ES, an Iraqi cyanobacterial strain, in public genbank databases will benefit the scientific community to understanding the potential of this cyanobacterial strain as a promising natural product producer.

Genome mining reveals secondary metabolites of Antarctic bacterium Streptomyces albidoflavus related to antimicrobial and antiproliferative activities.

The urgent need for new antimicrobials arises from antimicrobial resistance. Actinobacteria, especially Streptomyces genus, are responsible for production of numerous clinical antibiotics and anticancer agents. Genome mining reveals the biosynthetic gene clusters (BGCs) related to secondary metabolites and the genetic potential of a strain to produce natural products. However, this potential may not be expressed under laboratory conditions. In the present study, the Antarctic bacterium was taxonomically affiliated as Streptomyces albidoflavus ANT_B131 (CBMAI 1855). The crude extracts showed antimicrobial activity against both fungi, Gram-positive and Gram-negative bacteria and antiproliferative activity against five human tumor cell lines. Whole-genome sequencing reveals a genome size of 6.96Mb, and the genome mining identified 24 BGCs, representing 13.3% of the genome. The use of three culture media and three extraction methods reveals the expression and recovery of 20.8% of the BGCs. The natural products identified included compounds, such as surugamide A, surugamide D, desferrioxamine B + Al, desferrioxamine E, and ectoine. This study reveals the potential of S. albidoflavus ANT_B131 as a natural product producer. Yet, the diversity of culture media and extraction methods could enhance the BGCs expression and recovery of natural products, and could be a strategy to intensify the BGC expression of natural products.

Heterologous Biosynthesis of Complex Bacterial Natural Products in Burkholderia gladioli.

Bacterial natural products (NPs) are an indispensable source of drugs and biopesticides. Heterologous expression is an essential method for discovering bacterial NPs and the efficient biosynthesis of valuable NPs, but the chassis for Gram-negative bacterial NPs remains inadequate. In this study, we built a Burkholderiales mutant Burkholderia gladioli Δgbn::attB by introducing an integrated site (attB) to inactivate the native gladiolin (gbn) biosynthetic gene cluster, which stabilizes large foreign gene clusters and reduces the native metabolite profile. The growth and successful heterologous production of high-value NPs such as phylogenetically close Burkholderiales-derived antitumor polyketides (PKs) rhizoxins, phylogenetically distant Gammaproteobacteria-derived anti-MRSA (methicillin-resistant Staphylococcus aureus) antibiotics WAP-8294As, and Deltaproteobacteria-derived antitumor PKs disorazols demonstrate that this strain is a potential chassis for Gram-negative bacterial NPs. We further improved the yields of WAP-8294As through promoter insertions and precursor pathway overexpression based on heterologous expression in this strain. This study provides a robust bacterial chassis for genome mining, efficient production, and molecular engineering of bacterial NPs.

Genus Acrostalagmus: A Prolific Producer of Natural Products.

Acrostalagmus is known for its ability to produce numerous bioactive natural products, making it valuable in drug development. This review provides information on the sources, distribution, chemical structure types, biosynthesis, and biological activities of the compounds isolated from the genus Acrostalagmus in the family Plectosphaerellaceae from 1969 to 2022. The results show that 50% of the compounds isolated from Acrostalagmus are new natural products, and 82% of the natural products derived from this genus are from the marine Acrostalagmus. The compounds isolated from Acrostalagmus exhibit diverse structures, with alkaloids being of particular importance, accounting for 56% of the natural products derived from this genus. Furthermore, within the alkaloid class, 61% belong to the epipolythiodioxopiperazine family, highlighting the significance of epipolythiodioxopiperazine as a key characteristic structure within Acrostalagmus. Seventy-two percent of natural products derived from Acrostalagmus display bioactivities, with 50% of the bioactive compounds exhibiting more significant or comparable activities than their positive controls. Interestingly, 89% of potent active compounds are derived from marine fungi, demonstrating their promising potential for development. These findings underscore Acrostalagmus, particularly the marine-derived genus Acrostalagmusas, a valuable source of new bioactive secondary metabolites, and emphasize the vast resource importance of the ocean.

Discovery and Biosynthesis of the Cytotoxic Polyene Terpenomycin in Human Pathogenic Nocardia.

Nocardia are opportunistic human pathogens that can cause a range of debilitating and difficult to treat infections of the lungs, brain, skin, and soft tissues. Despite their close relationship to the well-known secondary metabolite-producing genus, Streptomyces, comparatively few natural products are known from the Nocardia, and even less is known about their involvement in the pathogenesis. Here, we combine chemistry, genomics, and molecular microbiology to reveal the production of terpenomycin, a new cytotoxic and antifungal polyene from a human pathogenic Nocardia terpenica isolate. We unveil the polyketide synthase (PKS) responsible for terpenomycin biosynthesis and show that it combines several unusual features, including "split", skipped, and iteratively used modules, and the use of the unusual extender unit methoxymalonate as a starter unit. To link genes to molecules, we constructed a transposon mutant library in N. terpenica, identifying a terpenomycin-null mutant with an inactivated terpenomycin PKS. Our findings show that the neglected actinomycetes have an unappreciated capacity for the production of bioactive molecules with unique biosynthetic pathways waiting to be uncovered and highlights these organisms as producers of diverse natural products.

Natural complex substances: From molecules to the molecular complexes. Analytical and technological advances for their definition and differentiation from the corresponding synthetic substances

Natural complex substances (NCSs) are a heterogeneous family of substances that are notably used as ingredients in several products classified as food supplements, medical devices, cosmetics and traditional medicines, according to the correspondent regulatory framework. The compositions of NCSs vary widely and hundreds to thousands of compounds can be present at the same time. A key concept is that NCSs are much more than the simple sum of the compounds that constitute them, in fact some emerging phenomena are the result of the supramolecular interaction of the constituents of the system. Therefore, close attention should be paid to produce and characterize these systems.Today many natural compounds are produced by chemical synthesis and are intentionally added to NCSs, or to formulated natural products, to enhance their properties, lowering their production costs. Market analysis shows a tendency of people to use products made with NCSs and, currently, products made with ingredients of natural origin only are not conveniently distinguishable from those containing compounds of synthetic origin. Furthermore, the uncertainty of the current European regulatory framework does not allow consumers to correctly differentiate and identify products containing only ingredients of natural origin.The high demand for specific and effective NCSs and their high-cost offer on the market, create the conditions to economically motivated sophistications, characterized by the addition of a cheap material to a more expensive one, just to increase profit. This type of practice can concern both the addition of less valuable natural materials and the addition of pure artificial compounds with the same structure as those naturally present.In this scenario, it becomes essential for producers of natural products to have advanced analytical techniques to evaluate the effective naturalness of NCSs. In fact, synthetically obtained compounds are not identical to their naturally occurring counterparts, due to the isotopic composition or chirality, as well as the presence of different trace metabolites (since pure substances in nature do not exist).For this reason, in this review, the main analytical tests that can be performed to differentiate natural compounds from their synthetic counterparts will be highlighted and the main analytical technologies will be described. At the same time, the main fingerprint techniques useful for characterizing the complexity of the NCSs, also allowing their identification and quali-quantitative evaluation, will be described.Furthermore, NCSs can be produced through different manufacturing processes, not all of which are on the same level of quality. In this review the most suitable technologies for green processes that operate according to physical extraction principles will be presented, as according to the authors they are the ones that come closest to creating more life-cycle compatible NCSs and that are well suited to the European green deal, a strategy with the aim of transforming the EU into a sustainable and resource-efficient society by 2050.

Evaluation of in Vitro Antioxidant Activity and L Asparaginase Enzyme Production of Four Endophytic Fungi Isolated from Acanthus Ilicifolius

The need for novel and useful bioactive secondary metabolites to help and relieve people from all aspects of human conditions is constantly expanding. Every plant tissue has a variety of endophytic fungi, which are thought to be highly effective producers of natural products. In this work, the determination of total phenolics, antioxidants, and L-asparaginase enzyme activity in four fungal endophytes associated with the mangrove plant Acanthus ilicifolius was evaluated. The study indicated that total phenolic content (1633+8.7 μg equivalent to gallic acid) and reducing power (0.96) were the highest for methanolic extracts of the isolate Aspergillus terreus while scavenging activity was highest for the isolate Colletotrichum xishuangbannaense (78.2+4.5 %). The enzyme activity of L-asparaginase was expressed predominantly by all the isolates except Colletotrichum xishuangbannaense. Maximum enzyme activities of 50.1 U/mL, 48.1 U/mL, and 47.7 U/mL were observed in Aspergillus terreus, Colletotrichum cobbiƫense, and Fusarium multiceps respectively. The current research demonstrated that mangrove-associated fungi have a high potential for producing bioactive molecules and L-asparaginase, which can be used as a possible source for the creation of anticancer drugs.

Comprehensive analysis of biosynthetic gene clusters in bacteria and discovery of Tumebacillus as a potential producer of natural products.

Limited microbial genera such as Streptomyces have served as sources of natural products (NPs), whereas most others have been less investigated. The vast accumulation of genomic data available in the NCBI database enables us to bioinformatically estimate the ability of other microbial groups to produce NPs. We analyzed 21,052 complete bacterial genome sequences using antiSMASH and compared the average numbers of biosynthetic gene clusters (BGCs) related to polyketides, non-ribosomal peptides, and/or terpenes biosynthesis at the genus level. Our bioinformatic analyses showed that Tumebacillus has 5-15 BGCs and is a promising NP producer. We searched for NPs from the culture broth of Tumebacillus permanentifrigoris JCM 14557T and found two novel compounds (tumebacin with anti-Bacillus activity and tumepyrazine) and identified two known compounds. Our results highlight the diversity of sources of NPs awaiting discovery.

Metabolomics Reveals a "Trimeric" γ-Actinorhodin from Streptomyces coelicolor M145.

Streptomyces coelicolor is a prolific producer of natural products and serves as a model organism for their study. It produces several pigmented antibiotics, the best-studied of which are the actinorhodins. We used a combination of liquid chromatography-mass spectrometry (LC-MS) and computational tools used for annotating the detected species (e. g., spectral matching, in-silico predictors, molecular networking) to identify putative new actinorhodin analogs. These studies led to the discovery of the first trimeric benzoisochromanequinone, θ-actinorhodin (1). Further metabolomics analysis revealed that the relative amounts of shunt products produced were similar between the two growth conditions explored. This suggests that, while substantially different products were being produced, the biosynthetic gene clusters were similarly active. Overall, this work describes the discovery of the first trimeric benzoisochromanequinone and explores the biosynthetic processes that might lead to its production by metabolomics analysis of relevant intermediates.

Lessons from assembling a microbial natural product and pre-fractionated extract library in an academic laboratory.

Microbial natural products are specialized metabolites that are sources of many bioactive compounds including antibiotics, antifungals, antiparasitics, anticancer agents, and probes of biology. The assembly of libraries of producers of natural products has traditionally been the province of the pharmaceutical industry. This sector has gathered significant historical collections of bacteria and fungi to identify new drug leads with outstanding outcomes-upwards of 60% of drug scaffolds originate from such libraries. Despite this success, the repeated rediscovery of known compounds and the resultant diminishing chemical novelty contributed to a pivot from this source of bioactive compounds toward more tractable synthetic compounds in the drug industry. The advent of advanced mass spectrometry tools, along with rapid whole genome sequencing and in silico identification of biosynthetic gene clusters that encode the machinery necessary for the synthesis of specialized metabolites, offers the opportunity to revisit microbial natural product libraries with renewed vigor. Assembling a suitable library of microbes and extracts for screening requires the investment of resources and the development of methods that have customarily been the proprietary purview of large pharmaceutical companies. Here, we report a perspective on our efforts to assemble a library of natural product-producing microbes and the establishment of methods to extract and fractionate bioactive compounds using resources available to most academic labs. We validate the library and approach through a series of screens for antimicrobial and cytotoxic agents. This work serves as a blueprint for establishing libraries of microbial natural product producers and bioactive extract fractions suitable for screens of bioactive compounds.

ANTAGONISTIC PROPERTIES OF THE BLACK SEA STREPTOMYCETES ISOLATED FROM THE FOULING OF SHELL ROCK AND MUSSELS

SummaryThe rapid emergence of resistance by bacterial and fungal pathogens is a serious problem in the health care system, which causes the search for new promising producers of antimicrobial natural products in various ecological niches. Aim. To determine the antagonistic activity of streptomycetes isolated from the biological fouling of natural shell rock and mussels of the Odesa gulf of the Black Sea. Methods. The antagonistic activity of 19 and 14 strains of streptomycetes isolated from the fouling of shell rock and mussels of the Odesa gulf, respectively, were investigated. Streptomycetes were pre-cultivated on agar media Gause 1, Gause 2 and oat agar with sea salt (2%) at a temperature of 30 °C for 10 days. Antagonistic activity against 12 test cultures was determined by the block method. Results. All isolated marine streptomycetes are antagonists of at least one strain of the indicator microorganism. Antibiotic activity depended on the source of the streptomycetes isolation, culture medium and properties of specific strains of both producers and test cultures. The best activity of streptomycetes strains from shell rock was shown after cultivation on Gause 1 medium, and streptomycetes from mussels – after cultivation on Gause 2 medium. The zones of no growth of sensitive indicators ranged from 12,4±0,3 mm to 20,6±0,2 mm (under the influence of streptomycetes from shell rock) and from 12,4±0,2 mm to 39,7±0,2 mm (under the influence of streptomycetes from mussels). Streptomyces sp. Lim 2.2 (strain from a shell rock) inhibited the growth of 8 test cultures, and strains from mussels Streptomyces sp. Myt 4b and Myt 7ch – 10 test cultures. Indicator strains of gram-positive bacteria were the most sensitive to all streptomycetes, in particular, strain Staphylococcus aureus ATCC 25923 was most inhibited by metabolites of Streptomyces spp. Myt 12a and Myt 12b. Conclusions. Antagonistic activity of streptomycetes isolated from the Black Sea depended on the source of isolation, pre-cultivation medium and properties of both producer strains and indicator microorganisms. The greatest activity of streptomycete strains from shell rock and mussels was shown after preliminary cultivation, respectively, on Gause 1 and Gause 2 media against gram-positive bacteria. The best antibiotic potential was found in strains of Streptomyces sp. Lim 2.2, Lim 4, Lim 5.1 and Lim 7.2, isolated from the fouling of shell rock, and strains of Streptomyces sp. Myt 7b, Myt 7ch, Myt 12a and Myt 12b isolated from mussels.

The Genus Chrysosporium: A Potential Producer of Natural Products

Chrysosporium, a genus of ascomycete fungi in the family Onygenaceae, has the ability to produce abundant new bioactive natural products, providing a structural foundation in drug development. This review includes the sources, distribution, biological activities and structural characteristics of the compounds isolated from Chrysosporium from 1984 to 2021. The results show that 66% of the compounds isolated from Chrysosporium are new natural products. More than half of the Chrysosporium-isolated compounds are from marine-derived Chrysosporium. The chemical structures of Chrysosporium-derived compounds have different skeletons, which are concentrated in alkaloids, polyketides, and lactones. Eighty percent of the natural products isolated from Chrysosporium have been found to have various biological activities, including cytotoxic, antibacterial, antifungal and enzyme-inhibitory activities. These results demonstrate the potential of Chrysosporium for producing new bioactive secondary metabolites, which can be used as the structural basis for developing new drugs.

Manipulation of fungal cell wall integrity to improve production of fungal natural products.

Fungi, as an important industrial microorganism, play an essential role in the production of natural products (NPs) due to their advantages of utilizing cheap raw materials as substrates and strong protein secretion ability. Although many metabolic engineering strategies have been adopted to enhance the biosynthetic pathway of NPs in fungi, the fungal cell wall as a natural barrier tissue is the final and key step that affects the efficiency of NPs synthesis. To date, many important progresses have been achieved in improving the synthesis of NPs by regulating the cell wall structure of fungi. In this review, we systematically summarize and discuss various strategies for modifying the cell wall structure of fungi to improve the synthesis of NPs. At first, the cell wall structure of different types of fungi is systematically described. Then, strategies to disrupt cell wall integrity (CWI) by regulating the synthesis of cell wall polysaccharides and binding proteins are summarized, which have been applied to improve the synthesis of NPs. In addition, we also summarize the studies on the regulation of CWI-related signaling pathway and the addition of exogenous components for regulating CWI to improve the synthesis of NPs. Finally, we propose the current challenges and essential strategies to usher in an era of more extensive manipulation of fungal CWI to improve the production of fungal NPs.

Draft Genomes of Halophilic Chromohalobacter and Halomonas Strains Isolated from Brines of The Carpathian Foreland, Poland.

Chromohalobacter and Halomonas are genera of bacterial microorganisms belonging to the group of halophiles. They are characterized by high diversity and the ability to produce bioproducts of biotechnological importance, such as ectoine, biosurfactants and carotenoids. Here, we report three draft genomes of Chromohalobacter and two draft genomes of Halomonas isolated from brines. The length of the genomes ranged from 3.6 Mbp to 3.8 Mbp, and GC content was in the 60.11%-66.46% range. None of the analysed genomes has been assigned to any previously known species of the genus Chromohalobacter or Halomonas. Phylogenetic analysis revealed that Chromohalobacter 296-RDG and Chromohalobacter 48-RD10 belonged to the same species, and Chromohalobacter 11-W is more distantly related to the other two analysed strains than to Chromohalobacter canadensis. Halomonas strains 11-S5 and 25-S5 were clustered together and located close to Halomonas ventosae. Functional analysis revealed BGCs related to ectoine production in all genomes analysed. This study increases our overall understanding of halophilic bacteria and is also consistent with the notion that members of this group have significant potential as useful natural product producers.