Novel Antibiotics from Actinomycetes

A special issue of Antibiotics (ISSN 2079-6382).

Deadline for manuscript submissions: closed (31 October 2020) | Viewed by 26100

Special Issue Editor


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Guest Editor
Department of Bioresources for Bioeconomy and Health Research, Leibniz Institute DSMZ-German Culture Collection for Microorganisms and Cell Cultures, 38124 Braunschweig, Germany
Interests: antibiotics; actinomycetes; biosynthesis; genome mining; genetic engineering; regulation; overproduction; synthetic biology; silent gene cluster; streptogramins
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Special Issue Information

Dear Colleagues,

Antimicrobial resistance has become one of the major threats to public health. In 2017, the WHO published a list of priority pathogens for which new antibiotics are urgently needed. Actinomycetes are well-known producers of antibiotics and the origin of most anti-infective drugs in use today. Thanks to the advent and continuing improvement of breakthrough technologies, such as next-generation sequencing techniques, OMICS technologies, novel cultivation strategies, and different high-tech chemical analysis methods, these bacteria will also be one of the most important sources for novel antibiotics in the decades to come.

This Special Issue of Antibiotics aims to provide a forum to disseminate the latest results on novel antibiotics from actinomycetes. Papers on the identification and characterization of novel antimicrobials from actinomycetes, new derivatives of natural compounds, promising new targets for antibiotics, strategies to overcome antibiotic resistances, synergism between different types of antibiotics, identification and characterization of new biosynthetic pathways for secondary metabolites, genetic engineering approaches for the production of novel natural compounds, and new techniques and strategies to identify antibiotics are welcome.

We kindly invite primary research articles as well as reviews of the state of the art. All articles will be peer-reviewed to ensure that high-quality contributions are included in this Special Issue.

Prof. Dr. Yvonne Mast
Guest Editor

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Keywords

  • antibiotics
  • actinomycetes
  • drug discovery
  • natural products
  • secondary metabolites
  • antibiotic resistance
  • antibiotic targets
  • genome mining
  • biosynthesis
  • drug combinations
  • natural product derivatization

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Published Papers (4 papers)

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Research

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13 pages, 13561 KiB  
Article
Angucycline-like Aromatic Polyketide from a Novel Streptomyces Species Reveals Freshwater Snail Physa acuta as Underexplored Reservoir for Antibiotic-Producing Actinomycetes
by Nasim Safaei, Yvonne Mast, Michael Steinert, Katharina Huber, Boyke Bunk and Joachim Wink
Antibiotics 2021, 10(1), 22; https://doi.org/10.3390/antibiotics10010022 - 29 Dec 2020
Cited by 7 | Viewed by 3951
Abstract
Antibiotic producers have mainly been isolated from soil, which often has led to the rediscovery of known compounds. In this study, we identified the freshwater snail Physa acuta as an unexplored source for new antibiotic producers. The bacterial diversity associated with the snail [...] Read more.
Antibiotic producers have mainly been isolated from soil, which often has led to the rediscovery of known compounds. In this study, we identified the freshwater snail Physa acuta as an unexplored source for new antibiotic producers. The bacterial diversity associated with the snail was characterized by a metagenomic approach using cultivation-independent high-throughput sequencing. Although Actinobacteria represented only 2% of the bacterial community, the focus was laid on the isolation of the genus Streptomyces due to its potential to produce antibiotics. Three Streptomyces strains (7NS1, 7NS2 and 7NS3) were isolated from P. acuta, and the antimicrobial activity of the crude extracts were tested against a selection of Gram-positive and Gram-negative bacteria and fungi. 7NS3 showed the strongest activity against Gram-positive bacteria and, thus, was selected for genome sequencing and a phylogenomic analysis. 7NS3 represents a novel Streptomyces species, which was deposited as Streptomyces sp. DSM 110735 at the Leibniz Institute-German Collection of Microorganisms and Cell Cultures (DSMZ). Bioassay-guided high-performance liquid chromatography (HPLC) and high-resolution electrospray ionization-mass spectrometry (HR-ESI-MS) analyses of crude extract fractions resulted in the detection of four compounds, one of which matched the compound characteristics of emycin A, an angucycline-like aromatic polyketide. Genome mining studies based on the whole-genome sequence of 7NS3 resulted in the identification of a gene cluster potentially coding for emycin A biosynthesis. Our study demonstrates that freshwater snails like P. acuta can represent promising reservoirs for the isolation of new antibiotic-producing actinobacterial species. Full article
(This article belongs to the Special Issue Novel Antibiotics from Actinomycetes)
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16 pages, 3951 KiB  
Article
Exploration of Chemical Diversity and Antitrypanosomal Activity of Some Red Sea-Derived Actinomycetes Using the OSMAC Approach Supported by LC-MS-Based Metabolomics and Molecular Modelling
by Noha M. Gamaleldin, Walid Bakeer, Ahmed M. Sayed, Yara I. Shamikh, Ahmed O. El-Gendy, Hossam M. Hassan, Hannes Horn, Usama Ramadan Abdelmohsen and Wael N. Hozzein
Antibiotics 2020, 9(9), 629; https://doi.org/10.3390/antibiotics9090629 - 22 Sep 2020
Cited by 20 | Viewed by 4823
Abstract
In the present study, we investigated the actinomycetes associated with the Red Sea-derived soft coral Sarcophyton glaucum in terms of biological and chemical diversity. Three strains were cultivated and identified to be members of genera Micromonospora, Streptomyces, and Nocardiopsis; out [...] Read more.
In the present study, we investigated the actinomycetes associated with the Red Sea-derived soft coral Sarcophyton glaucum in terms of biological and chemical diversity. Three strains were cultivated and identified to be members of genera Micromonospora, Streptomyces, and Nocardiopsis; out of them, Micromonospora sp. UR17 was putatively characterized as a new species. In order to explore the chemical diversity of these actinobacteria as far as possible, they were subjected to a series of fermentation experiments under altering conditions, that is, solid and liquid fermentation along with co-fermentation with a mycolic acid-containing strain, namely Nocardia sp. UR23. Each treatment was found to affect these actinomycetes differently in terms of biological activity (i.e., antitrypanosomal activity) and chemical profiles evidenced by LC-HRES-MS-based metabolomics and multivariate analysis. Thereafter, orthogonal projections to latent structures discriminant analysis (OPLS-DA) suggested a number of metabolites to be associated with the antitrypanosomal activity of the active extracts. The subsequent in silico screenings (neural networking-based and docking-based) further supported the OPLS-DA results and prioritized desferrioxamine B (3), bafilomycin D (10), and bafilomycin A1 (11) as possible antitrypanosomal agents. Our approach in this study can be applied as a primary step in the exploration of bioactive natural products, particularly those from actinomycetes. Full article
(This article belongs to the Special Issue Novel Antibiotics from Actinomycetes)
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18 pages, 4039 KiB  
Article
The Bristol Sponge Microbiome Collection: A Unique Repository of Deep-Sea Microorganisms and Associated Natural Products
by Sam E. Williams, Henry L. Stennett, Catherine R. Back, Kavita Tiwari, Jorge Ojeda Gomez, Martin R. Challand, Katharine R. Hendry, James Spencer, Angela E. Essex-Lopresti, Christine L. Willis, Paul Curnow and Paul R. Race
Antibiotics 2020, 9(8), 509; https://doi.org/10.3390/antibiotics9080509 - 13 Aug 2020
Cited by 9 | Viewed by 6308
Abstract
The deep ocean is the largest habitat for life on Earth, though the microorganisms that occupy this unique environmental niche remain largely unexplored. Due to the significant logistical and operational challenges associated with accessing the deep ocean, bioprospecting programmes that seek to generate [...] Read more.
The deep ocean is the largest habitat for life on Earth, though the microorganisms that occupy this unique environmental niche remain largely unexplored. Due to the significant logistical and operational challenges associated with accessing the deep ocean, bioprospecting programmes that seek to generate novel products from marine organisms have, to date, focused predominantly on samples recovered from shallow seas. For this reason, the deep ocean remains a largely untapped resource of novel microbiological life and associated natural products. Here we report the establishment of the Bristol Sponge Microbiome Collection (BISECT), a unique repository of deep-sea microorganisms and associated metabolites isolated from the microbiota of marine sponges, recovered from previously unsurveyed regions of the mid Atlantic Ocean, at depths of 0.3–3 km. An integrated biodiscovery pipeline comprising molecular, genetic, bioinformatic and analytical tools is also described, which is being applied to interrogate this collection. The potential of this approach is illustrated using data reporting our initial efforts to identify antimicrobial natural product lead compounds. Prospects for the use of BISECT to address allied pharmaceutical needs, along with mechanisms of access to the collection are also discussed Full article
(This article belongs to the Special Issue Novel Antibiotics from Actinomycetes)
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Review

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31 pages, 1492 KiB  
Review
An Update on Molecular Tools for Genetic Engineering of Actinomycetes—The Source of Important Antibiotics and Other Valuable Compounds
by Lena Mitousis, Yvonne Thoma and Ewa M. Musiol-Kroll
Antibiotics 2020, 9(8), 494; https://doi.org/10.3390/antibiotics9080494 - 8 Aug 2020
Cited by 24 | Viewed by 9827
Abstract
The first antibiotic-producing actinomycete (Streptomyces antibioticus) was described by Waksman and Woodruff in 1940. This discovery initiated the “actinomycetes era”, in which several species were identified and demonstrated to be a great source of bioactive compounds. However, the remarkable group of [...] Read more.
The first antibiotic-producing actinomycete (Streptomyces antibioticus) was described by Waksman and Woodruff in 1940. This discovery initiated the “actinomycetes era”, in which several species were identified and demonstrated to be a great source of bioactive compounds. However, the remarkable group of microorganisms and their potential for the production of bioactive agents were only partially exploited. This is caused by the fact that the growth of many actinomycetes cannot be reproduced on artificial media at laboratory conditions. In addition, sequencing, genome mining and bioactivity screening disclosed that numerous biosynthetic gene clusters (BGCs), encoded in actinomycetes genomes are not expressed and thus, the respective potential products remain uncharacterized. Therefore, a lot of effort was put into the development of technologies that facilitate the access to actinomycetes genomes and activation of their biosynthetic pathways. In this review, we mainly focus on molecular tools and methods for genetic engineering of actinomycetes that have emerged in the field in the past five years (2015–2020). In addition, we highlight examples of successful application of the recently developed technologies in genetic engineering of actinomycetes for activation and/or improvement of the biosynthesis of secondary metabolites. Full article
(This article belongs to the Special Issue Novel Antibiotics from Actinomycetes)
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