Marine Drugs

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18 pages, 2987 KiB

Open AccessArticle

Micrococcin P1 and P2 from Epibiotic Bacteria Associated with Isolates of Moorea producens from Kenya

by Thomas Dzeha, Michael John Hall and James Grant Burgess

Mar. Drugs 2022, 20(2), 128; https://doi.org/10.3390/md20020128 - 7 Feb 2022

Cited by 1 | Viewed by 3286

Abstract

Epibiotic bacteria associated with the filamentous marine cyanobacterium Moorea producens were explored as a novel source of antibiotics and to establish whether they can produce cyclodepsipeptides on their own. Here, we report the isolation of micrococcin P1 (1) (C₄₈H [...] Read more.

Epibiotic bacteria associated with the filamentous marine cyanobacterium Moorea producens were explored as a novel source of antibiotics and to establish whether they can produce cyclodepsipeptides on their own. Here, we report the isolation of micrococcin P1 (1) (C₄₈H₄₉N₁₃O₉S₆; obs. m/z 1144.21930/572.60381) and micrococcin P2 (2) (C₄₈H₄₇N₁₃O₉S₆; obs. m/z 1142.20446/571.60370) from a strain of Bacillus marisflavi isolated from M. producens’ filaments. Interestingly, most bacteria isolated from M. producens’ filaments were found to be human pathogens. Stalked diatoms on the filaments suggested a possible terrestrial origin of some epibionts. CuSO₄·5H₂O assisted differential genomic DNA isolation and phylogenetic analysis showed that a Kenyan strain of M. producens differed from L. majuscula strain CCAP 1446/4 and L. majuscula clones. Organic extracts of the epibiotic bacteria Pseudoalteromonas carrageenovora and Ochrobactrum anthropi did not produce cyclodepsipeptides. Further characterization of 24 Firmicutes strains from M. producens identified extracts of B. marisflavi as most active. Our results showed that the genetic basis for synthesizing micrococcin P1 (1), discovered in Bacillus cereus ATCC 14579, is species/strain-dependent and this reinforces the need for molecular identification of M. producens species worldwide and their epibionts. These findings indicate that M. producens-associated bacteria are an overlooked source of antimicrobial compounds. Full article

(This article belongs to the Special Issue Natural Product Genomics and Metabolomics of Marine Bacteria)

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18 pages, 5063 KiB

Open AccessArticle

Metabolomic Characterization of a cf. Neolyngbya Cyanobacterium from the South China Sea Reveals Wenchangamide A, a Lipopeptide with In Vitro Apoptotic Potential in Colon Cancer Cells

by Lijian Ding, Rinat Bar-Shalom, Dikla Aharonovich, Naoaki Kurisawa, Gaurav Patial, Shuang Li, Shan He, Xiaojun Yan, Arihiro Iwasaki, Kiyotake Suenaga, Chengcong Zhu, Haixi Luo, Fuli Tian, Fuad Fares, C. Benjamin Naman and Tal Luzzatto-Knaan

Mar. Drugs 2021, 19(7), 397; https://doi.org/10.3390/md19070397 - 16 Jul 2021

Cited by 8 | Viewed by 4532

Abstract

Metabolomics can be used to study complex mixtures of natural products, or secondary metabolites, for many different purposes. One productive application of metabolomics that has emerged in recent years is the guiding direction for isolating molecules with structural novelty through analysis of untargeted [...] Read more.

Metabolomics can be used to study complex mixtures of natural products, or secondary metabolites, for many different purposes. One productive application of metabolomics that has emerged in recent years is the guiding direction for isolating molecules with structural novelty through analysis of untargeted LC-MS/MS data. The metabolomics-driven investigation and bioassay-guided fractionation of a biomass assemblage from the South China Sea dominated by a marine filamentous cyanobacteria, cf. Neolyngbya sp., has led to the discovery of a natural product in this study, wenchangamide A (1). Wenchangamide A was found to concentration-dependently cause fast-onset apoptosis in HCT116 human colon cancer cells in vitro (24 h IC₅₀ = 38 μM). Untargeted metabolomics, by way of MS/MS molecular networking, was used further to generate a structural proposal for a new natural product analogue of 1, here coined wenchangamide B, which was present in the organic extract and bioactive sub-fractions of the biomass examined. The wenchangamides are of interest for anticancer drug discovery, and the characterization of these molecules will facilitate the future discovery of related natural products and development of synthetic analogues. Full article

(This article belongs to the Special Issue Natural Product Genomics and Metabolomics of Marine Bacteria)

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21 pages, 3309 KiB

Open AccessArticle

Genome Mining for Antimicrobial Compounds in Wild Marine Animals-Associated Enterococci

by Janira Prichula, Muriel Primon-Barros, Romeu C. Z. Luz, Ícaro M. S. Castro, Thiago G. S. Paim, Maurício Tavares, Rodrigo Ligabue-Braun, Pedro A. d’Azevedo, Jeverson Frazzon, Ana P. G. Frazzon, Adriana Seixas and Michael S. Gilmore

Mar. Drugs 2021, 19(6), 328; https://doi.org/10.3390/md19060328 - 6 Jun 2021

Cited by 18 | Viewed by 4967

Abstract

New ecosystems are being actively mined for new bioactive compounds. Because of the large amount of unexplored biodiversity, bacteria from marine environments are especially promising. Further, host-associated microbes are of special interest because of their low toxicity and compatibility with host health. Here, [...] Read more.

New ecosystems are being actively mined for new bioactive compounds. Because of the large amount of unexplored biodiversity, bacteria from marine environments are especially promising. Further, host-associated microbes are of special interest because of their low toxicity and compatibility with host health. Here, we identified and characterized biosynthetic gene clusters encoding antimicrobial compounds in host-associated enterococci recovered from fecal samples of wild marine animals remote from human-affected ecosystems. Putative biosynthetic gene clusters in the genomes of 22 Enterococcus strains of marine origin were predicted using antiSMASH5 and Bagel4 bioinformatic software. At least one gene cluster encoding a putative bioactive compound precursor was identified in each genome. Collectively, 73 putative antimicrobial compounds were identified, including 61 bacteriocins (83.56%), 10 terpenes (13.70%), and 2 (2.74%) related to putative nonribosomal peptides (NRPs). Two of the species studied, Enterococcus avium and Enterococcus mundtti, are rare causes of human disease and were found to lack any known pathogenic determinants but yet possessed bacteriocin biosynthetic genes, suggesting possible additional utility as probiotics. Wild marine animal-associated enterococci from human-remote ecosystems provide a potentially rich source for new antimicrobial compounds of therapeutic and industrial value and potential probiotic application. Full article

(This article belongs to the Special Issue Natural Product Genomics and Metabolomics of Marine Bacteria)

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27 pages, 3631 KiB

Open AccessArticle

Mining Indonesian Microbial Biodiversity for Novel Natural Compounds by a Combined Genome Mining and Molecular Networking Approach

by Ira Handayani, Hamada Saad, Shanti Ratnakomala, Puspita Lisdiyanti, Wien Kusharyoto, Janina Krause, Andreas Kulik, Wolfgang Wohlleben, Saefuddin Aziz, Harald Gross, Athina Gavriilidou, Nadine Ziemert and Yvonne Mast

Mar. Drugs 2021, 19(6), 316; https://doi.org/10.3390/md19060316 - 28 May 2021

Cited by 18 | Viewed by 5902

Abstract

Indonesia is one of the most biodiverse countries in the world and a promising resource for novel natural compound producers. Actinomycetes produce about two thirds of all clinically used antibiotics. Thus, exploiting Indonesia’s microbial diversity for actinomycetes may lead to the discovery of [...] Read more.

Indonesia is one of the most biodiverse countries in the world and a promising resource for novel natural compound producers. Actinomycetes produce about two thirds of all clinically used antibiotics. Thus, exploiting Indonesia’s microbial diversity for actinomycetes may lead to the discovery of novel antibiotics. A total of 422 actinomycete strains were isolated from three different unique areas in Indonesia and tested for their antimicrobial activity. Nine potent bioactive strains were prioritized for further drug screening approaches. The nine strains were cultivated in different solid and liquid media, and a combination of genome mining analysis and mass spectrometry (MS)-based molecular networking was employed to identify potential novel compounds. By correlating secondary metabolite gene cluster data with MS-based molecular networking results, we identified several gene cluster-encoded biosynthetic products from the nine strains, including naphthyridinomycin, amicetin, echinomycin, tirandamycin, antimycin, and desferrioxamine B. Moreover, 16 putative ion clusters and numerous gene clusters were detected that could not be associated with any known compound, indicating that the strains can produce novel secondary metabolites. Our results demonstrate that sampling of actinomycetes from unique and biodiversity-rich habitats, such as Indonesia, along with a combination of gene cluster networking and molecular networking approaches, accelerates natural product identification. Full article

(This article belongs to the Special Issue Natural Product Genomics and Metabolomics of Marine Bacteria)

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17 pages, 3215 KiB

Open AccessArticle

Genome Reduction and Secondary Metabolism of the Marine Sponge-Associated Cyanobacterium Leptothoe

by Despoina Konstantinou, Rafael V. Popin, David P. Fewer, Kaarina Sivonen and Spyros Gkelis

Mar. Drugs 2021, 19(6), 298; https://doi.org/10.3390/md19060298 - 24 May 2021

Cited by 4 | Viewed by 3822

Abstract

Sponges form symbiotic relationships with diverse and abundant microbial communities. Cyanobacteria are among the most important members of the microbial communities that are associated with sponges. Here, we performed a genus-wide comparative genomic analysis of the newly described marine benthic cyanobacterial genus Leptothoe [...] Read more.

Sponges form symbiotic relationships with diverse and abundant microbial communities. Cyanobacteria are among the most important members of the microbial communities that are associated with sponges. Here, we performed a genus-wide comparative genomic analysis of the newly described marine benthic cyanobacterial genus Leptothoe (Synechococcales). We obtained draft genomes from Le. kymatousa TAU-MAC 1615 and Le. spongobia TAU-MAC 1115, isolated from marine sponges. We identified five additional Leptothoe genomes, host-associated or free-living, using a phylogenomic approach, and the comparison of all genomes showed that the sponge-associated strains display features of a symbiotic lifestyle. Le. kymatousa and Le. spongobia have undergone genome reduction; they harbored considerably fewer genes encoding for (i) cofactors, vitamins, prosthetic groups, pigments, proteins, and amino acid biosynthesis; (ii) DNA repair; (iii) antioxidant enzymes; and (iv) biosynthesis of capsular and extracellular polysaccharides. They have also lost several genes related to chemotaxis and motility. Eukaryotic-like proteins, such as ankyrin repeats, playing important roles in sponge-symbiont interactions, were identified in sponge-associated Leptothoe genomes. The sponge-associated Leptothoe stains harbored biosynthetic gene clusters encoding novel natural products despite genome reduction. Comparisons of the biosynthetic capacities of Leptothoe with chemically rich cyanobacteria revealed that Leptothoe is another promising marine cyanobacterium for the biosynthesis of novel natural products. Full article

(This article belongs to the Special Issue Natural Product Genomics and Metabolomics of Marine Bacteria)

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24 pages, 25204 KiB

Open AccessArticle

An Integrative Bioinformatic Analysis for Keratinase Detection in Marine-Derived Streptomyces

by Ricardo Valencia, Valentina González, Agustina Undabarrena, Leonardo Zamora-Leiva, Juan A. Ugalde and Beatriz Cámara

Mar. Drugs 2021, 19(6), 286; https://doi.org/10.3390/md19060286 - 21 May 2021

Cited by 5 | Viewed by 3386

Abstract

Keratinases present promising biotechnological applications, due to their ability to degrade keratin. Streptomyces appears as one of the main sources of these enzymes, but complete genome sequences of keratinolytic bacteria are still limited. This article reports the complete genomes of three marine-derived streptomycetes [...] Read more.

Keratinases present promising biotechnological applications, due to their ability to degrade keratin. Streptomyces appears as one of the main sources of these enzymes, but complete genome sequences of keratinolytic bacteria are still limited. This article reports the complete genomes of three marine-derived streptomycetes that show different levels of feather keratin degradation, with high (strain G11C), low (strain CHD11), and no (strain Vc74B-19) keratinolytic activity. A multi-step bioinformatics approach is described to explore genes encoding putative keratinases in these genomes. Despite their differential keratinolytic activity, multiplatform annotation reveals similar quantities of ORFs encoding putative proteases in strains G11C, CHD11, and Vc74B-19. Comparative genomics classified these putative proteases into 140 orthologous groups and 17 unassigned orthogroup peptidases belonging to strain G11C. Similarity network analysis revealed three network communities of putative peptidases related to known keratinases of the peptidase families S01, S08, and M04. When combined with the prediction of cellular localization and phylogenetic reconstruction, seven putative keratinases from the highly keratinolytic strain Streptomyces sp. G11C are identified. To our knowledge, this is the first multi-step bioinformatics analysis that complements comparative genomics with phylogeny and cellular localization prediction, for the prediction of genes encoding putative keratinases in streptomycetes. Full article

(This article belongs to the Special Issue Natural Product Genomics and Metabolomics of Marine Bacteria)

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17 pages, 1197 KiB

Open AccessArticle

Chitin Degradation Machinery and Secondary Metabolite Profiles in the Marine Bacterium Pseudoalteromonas rubra S4059

by Xiyan Wang, Thomas Isbrandt, Mikael Lenz Strube, Sara Skøtt Paulsen, Maike Wennekers Nielsen, Yannick Buijs, Erwin M. Schoof, Thomas Ostenfeld Larsen, Lone Gram and Sheng-Da Zhang

Mar. Drugs 2021, 19(2), 108; https://doi.org/10.3390/md19020108 - 12 Feb 2021

Cited by 15 | Viewed by 4973

Abstract

Genome mining of pigmented Pseudoalteromonas has revealed a large potential for the production of bioactive compounds and hydrolytic enzymes. The purpose of the present study was to explore this bioactivity potential in a potent antibiotic and enzyme producer, Pseudoalteromonas rubra strain S4059. Proteomic [...] Read more.

Genome mining of pigmented Pseudoalteromonas has revealed a large potential for the production of bioactive compounds and hydrolytic enzymes. The purpose of the present study was to explore this bioactivity potential in a potent antibiotic and enzyme producer, Pseudoalteromonas rubra strain S4059. Proteomic analyses (data are available via ProteomeXchange with identifier PXD023249) indicated that a highly efficient chitin degradation machinery was present in the red-pigmented P. rubra S4059 when grown on chitin. Four GH18 chitinases and two GH20 hexosaminidases were significantly upregulated under these conditions. GH19 chitinases, which are not common in bacteria, are consistently found in pigmented Pseudoalteromonas, and in S4059, GH19 was only detected when the bacterium was grown on chitin. To explore the possible role of GH19 in pigmented Pseudoalteromonas, we developed a protocol for genetic manipulation of S4059 and deleted the GH19 chitinase, and compared phenotypes of the mutant and wild type. However, none of the chitin degrading ability, secondary metabolite profile, or biofilm-forming capacity was affected by GH19 deletion. In conclusion, we developed a genetic manipulation protocol that can be used to unravel the bioactive potential of pigmented pseudoalteromonads. An efficient chitinolytic enzyme cocktail was identified in S4059, suggesting that this strain could be a candidate with industrial potential. Full article

(This article belongs to the Special Issue Natural Product Genomics and Metabolomics of Marine Bacteria)

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21 pages, 4204 KiB

Open AccessArticle

Comparative Metabologenomics Analysis of Polar Actinomycetes

by Sylvia Soldatou, Grímur Hjörleifsson Eldjárn, Andrew Ramsay, Justin J. J. van der Hooft, Alison H. Hughes, Simon Rogers and Katherine R. Duncan

Mar. Drugs 2021, 19(2), 103; https://doi.org/10.3390/md19020103 - 10 Feb 2021

Cited by 22 | Viewed by 8258

Abstract

Biosynthetic and chemical datasets are the two major pillars for microbial drug discovery in the omics era. Despite the advancement of analysis tools and platforms for multi-strain metabolomics and genomics, linking these information sources remains a considerable bottleneck in strain prioritisation and natural [...] Read more.

Biosynthetic and chemical datasets are the two major pillars for microbial drug discovery in the omics era. Despite the advancement of analysis tools and platforms for multi-strain metabolomics and genomics, linking these information sources remains a considerable bottleneck in strain prioritisation and natural product discovery. In this study, molecular networking of the 100 metabolite extracts derived from applying the OSMAC approach to 25 Polar bacterial strains, showed growth media specificity and potential chemical novelty was suggested. Moreover, the metabolite extracts were screened for antibacterial activity and promising selective bioactivity against drug-persistent pathogens such as Klebsiella pneumoniae and Acinetobacter baumannii was observed. Genome sequencing data were combined with metabolomics experiments in the recently developed computational approach, NPLinker, which was used to link BGC and molecular features to prioritise strains for further investigation based on biosynthetic and chemical information. Herein, we putatively identified the known metabolites ectoine and chrloramphenicol which, through NPLinker, were linked to their associated BGCs. The metabologenomics approach followed in this study can potentially be applied to any large microbial datasets for accelerating the discovery of new (bioactive) specialised metabolites. Full article

(This article belongs to the Special Issue Natural Product Genomics and Metabolomics of Marine Bacteria)

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13 pages, 1472 KiB

Open AccessArticle

Anti-Infective and Antiviral Activity of Valinomycin and Its Analogues from a Sea Cucumber-Associated Bacterium, Streptomyces sp. SV 21

by Joko T. Wibowo, Matthias Y. Kellermann, Matthias Köck, Masteria Y. Putra, Tutik Murniasih, Kathrin I. Mohr, Joachim Wink, Dimas F. Praditya, Eike Steinmann and Peter J. Schupp

Mar. Drugs 2021, 19(2), 81; https://doi.org/10.3390/md19020081 - 2 Feb 2021

Cited by 22 | Viewed by 3730

Abstract

The manuscript investigated the isolation, characterization and anti-infective potential of valinomycin (3), streptodepsipeptide P11A (2), streptodepsipeptide P11B (1), and one novel valinomycin analogue, streptodepsipeptide SV21 (4), which were all produced by the Gram-positive strain Streptomyces [...] Read more.

The manuscript investigated the isolation, characterization and anti-infective potential of valinomycin (3), streptodepsipeptide P11A (2), streptodepsipeptide P11B (1), and one novel valinomycin analogue, streptodepsipeptide SV21 (4), which were all produced by the Gram-positive strain Streptomycescavourensis SV 21. Although the exact molecular weight and major molecular fragments were recently reported for compound 4, its structure elucidation was not based on compound isolation and spectroscopic techniques. We successfully isolated and elucidated the structure based on the MS² fragmentation pathways as well as ¹H and ¹³C NMR spectra and found that the previously reported structure of compound 4 differs from our analysis. Our findings showed the importance of isolation and structure elucidation of bacterial compounds in the era of fast omics technologies. The here performed anti-infective assays showed moderate to potent activity against fungi, multi drug resistant (MDR) bacteria and infectivity of the Hepatitis C Virus (HCV). While compounds 2, 3 and 4 revealed potent antiviral activity, the observed minor cytotoxicity needs further investigation. Furthermore, the here performed anti-infective assays disclosed that the symmetry of the valinomycin molecule is most important for its bioactivity, a fact that has not been reported so far. Full article

(This article belongs to the Special Issue Natural Product Genomics and Metabolomics of Marine Bacteria)

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15 pages, 6191 KiB

Open AccessArticle

Sustainable Low-Volume Analysis of Environmental Samples by Semi-Automated Prioritization of Extracts for Natural Product Research (SeaPEPR)

by Riyanti, Michael Marner, Christoph Hartwig, Maria A. Patras, Stevy I. M. Wodi, Frets J. Rieuwpassa, Frans G. Ijong, Walter Balansa and Till F. Schäberle

Mar. Drugs 2020, 18(12), 649; https://doi.org/10.3390/md18120649 - 17 Dec 2020

Cited by 8 | Viewed by 3604

Abstract

The discovery of novel natural products (NPs) that will serve as lead structures has to be an ongoing effort to fill the respective development pipelines. However, identification of NPs, which possess a potential for application in e.g., the pharma or agro sector, must [...] Read more.

The discovery of novel natural products (NPs) that will serve as lead structures has to be an ongoing effort to fill the respective development pipelines. However, identification of NPs, which possess a potential for application in e.g., the pharma or agro sector, must be as cost effective and fast as possible. Furthermore, the amount of sample available for initial testing is usually very limited, not least because of the fact that the impact on the environment, i.e., the sampled biosystem, should be kept minimal. Here, our pipeline SeaPEPR is described, in which a primary bioactivity screening of crude extracts is combined with the analysis of their metabolic fingerprint. This enabled prioritization of samples for subsequent microfractionation and dereplication of the active compounds early in the workflow. As a case study, 76 marine sponge-derived extracts were screened against a microbial screening panel. Thereunder, human pathogenic bacteria (Escherichia coli ATCC35218 and Staphylococcus aureus ATCC33592) and yeast (Candida albicans FH2173), as well as the phytopathogenic fungus Septoria tritici MUCL45407. Overall, nine extracts revealed activity against at least one test organism. Metabolic fingerprinting enabled assigning four active extracts into one metabolic group; therefore, one representative was selected for subsequent microfractionation. Dereplication of the active fractions showed a new dibrominated aplysinopsin and a hypothetical chromazonarol stereoisomer derivative. Furthermore, inhibitory activity against the common plant pest Septoria tritici was discovered for NPs of marine origin. Full article

(This article belongs to the Special Issue Natural Product Genomics and Metabolomics of Marine Bacteria)

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25 pages, 3572 KiB

Open AccessArticle

Applying a Chemogeographic Strategy for Natural Product Discovery from the Marine Cyanobacterium Moorena bouillonii

by Christopher A. Leber, C. Benjamin Naman, Lena Keller, Jehad Almaliti, Eduardo J. E. Caro-Diaz, Evgenia Glukhov, Valsamma Joseph, T. P. Sajeevan, Andres Joshua Reyes, Jason S. Biggs, Te Li, Ye Yuan, Shan He, Xiaojun Yan and William H. Gerwick

Mar. Drugs 2020, 18(10), 515; https://doi.org/10.3390/md18100515 - 14 Oct 2020

Cited by 9 | Viewed by 4202

Abstract

The tropical marine cyanobacterium Moorena bouillonii occupies a large geographic range across the Indian and Western Tropical Pacific Oceans and is a prolific producer of structurally unique and biologically active natural products. An ensemble of computational approaches, including the creation of the ORCA [...] Read more.

The tropical marine cyanobacterium Moorena bouillonii occupies a large geographic range across the Indian and Western Tropical Pacific Oceans and is a prolific producer of structurally unique and biologically active natural products. An ensemble of computational approaches, including the creation of the ORCA (Objective Relational Comparative Analysis) pipeline for flexible MS¹ feature detection and multivariate analyses, were used to analyze various M. bouillonii samples. The observed chemogeographic patterns suggested the production of regionally specific natural products by M. bouillonii. Analyzing the drivers of these chemogeographic patterns allowed for the identification, targeted isolation, and structure elucidation of a regionally specific natural product, doscadenamide A (1). Analyses of MS² fragmentation patterns further revealed this natural product to be part of an extensive family of herein annotated, proposed natural structural analogs (doscadenamides B–J, 2–10); the ensemble of structures reflect a combinatorial biosynthesis using nonribosomal peptide synthetase (NRPS) and polyketide synthase (PKS) components. Compound 1 displayed synergistic in vitro cancer cell cytotoxicity when administered with lipopolysaccharide (LPS). These discoveries illustrate the utility in leveraging chemogeographic patterns for prioritizing natural product discovery efforts. Full article

(This article belongs to the Special Issue Natural Product Genomics and Metabolomics of Marine Bacteria)

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Review

Jump to: Research

10 pages, 2699 KiB

Open AccessReview

Coupling Mass Spectral and Genomic Information to Improve Bacterial Natural Product Discovery Workflows

by Max Crüsemann

Mar. Drugs 2021, 19(3), 142; https://doi.org/10.3390/md19030142 - 5 Mar 2021

Cited by 10 | Viewed by 3772

Abstract

Bacterial natural products possess potent bioactivities and high structural diversity and are typically encoded in biosynthetic gene clusters. Traditional natural product discovery approaches rely on UV- and bioassay-guided fractionation and are limited in terms of dereplication. Recent advances in mass spectrometry, sequencing and [...] Read more.

Bacterial natural products possess potent bioactivities and high structural diversity and are typically encoded in biosynthetic gene clusters. Traditional natural product discovery approaches rely on UV- and bioassay-guided fractionation and are limited in terms of dereplication. Recent advances in mass spectrometry, sequencing and bioinformatics have led to large-scale accumulation of genomic and mass spectral data that is increasingly used for signature-based or correlation-based mass spectrometry genome mining approaches that enable rapid linking of metabolomic and genomic information to accelerate and rationalize natural product discovery. In this mini-review, these approaches are presented, and discovery examples provided. Finally, future opportunities and challenges for paired omics-based natural products discovery workflows are discussed. Full article

(This article belongs to the Special Issue Natural Product Genomics and Metabolomics of Marine Bacteria)

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