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Microorganisms
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Natural Products from Streptomyces
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Natural Products from Streptomyces

A special issue of Microorganisms (ISSN 2076-2607). This special issue belongs to the section "Microbial Biotechnology".

Deadline for manuscript submissions: closed (15 October 2020) | Viewed by 28011

Special Issue Editor

Prof. Dr. Jae Kyung Sohng

E-Mail Website
Guest Editor
Department of Life Science and Biochemical Engineering, Sun Moon University, Chungnam, Korea
Interests: natural products; actinomycetes; streptomyces; flavonoids; antibiotics; anticancer drugs; metabolic engineering; synthetic biology; enzymatic modifications
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Natural products (NPs) derived from microorganisms are important starting points for drug discovery and development. Streptomyces are recognized as the most notable microorganisms for the production of NPs, having valuable pharmaceutical applications due to their considerable diversity in structure bioactivities. Advances in the isolation of such NPs, precise structural identification, and high-throughput screening of their bioactivities have facilitated the discovery of compounds with novel activities. Moreover, recent advances in genome sequencing and analysis have enabled the connection of secondary metabolites to their respective biosynthetic genetic codes, also known as “genome mining”. In addition, the application of metabolic engineering, synthetic biology tools, and genome engineering has revolutionized the discovery of novel NPs with novel functionalities. Hence, this Special Issue will cover all aspects of the discovery of NPs from Streptomyces.

  • Isolation of novel NPs by modulation of the growth condition, co-culture, and activation of the cryptic biosynthetic pathway;
  • Genome mining for deducing the biosynthetic gene clusters for novel NPs;
  • Metabolic engineering, synthetic biology, and genome engineering for production and structural modification of NPs;
  • Combinatorial biosynthesis, mutasynthesis, and enzymatic modifications for generating new derivatives of NPs;
  • Biological activities and mode of action of NPs.

Prof. Dr. Jae Kyung Sohng
Guest Editor

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Keywords

  • streptomyces natural products
  • biosynthetic pathway
  • genome mining
  • metabolic engineering
  • synthetic biology tools
  • natural product modifications
  • biological activities

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Published Papers (6 papers)

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Research

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15 pages, 22705 KiB  
Article
An Actinobacterial Isolate, Streptomyces sp. YX44, Produces Broad-Spectrum Antibiotics That Strongly Inhibit Staphylococcus aureus
by Tien-Lin Chang, Tzu-Wen Huang, Ying-Xuan Wang, Chang-Pan Liu, Ralph Kirby, Chien-Ming Chu and Chih-Hung Huang
Microorganisms 2021, 9(3), 630; https://doi.org/10.3390/microorganisms9030630 - 18 Mar 2021
Cited by 9 | Viewed by 3938
Abstract
The need for new antibiotics is increasing due to their overuse, and antibiotic resistance has become one of the major threats worldwide to public health, food safety, and clinical treatment. In this study, we describe an actinobacterial isolate, YX44, which belongs to the [...] Read more.
The need for new antibiotics is increasing due to their overuse, and antibiotic resistance has become one of the major threats worldwide to public health, food safety, and clinical treatment. In this study, we describe an actinobacterial isolate, YX44, which belongs to the genus Streptomyces. This Streptomyces was isolated from a drinking pipe located in Osaka, Japan, and has the ability to inhibit Gram-positive bacteria, Gram-negative bacteria, and various fungi. YX44 fermentation broth shows strong activity against Escherichia coli and Staphylococcus aureus, as well as also inhibiting clinical isolates of multidrug-resistant Staphylococcus aureus. The YX44 antibacterial substances in the broth are relatively heat-stable, show high stability from the pH range 1 to 11, and have good solubility in both organic and non-organic solvents. Size-exclusion chromatography revealed that the YX44 antibacterial compounds are less than 1000 Da in size. LC-MS was able to identify three possible candidate molecules with molecular weights of 308, 365, 460, and 653 g/mol; none of these sizes correspond to any well-known antibiotics. Our results show that Streptomyces sp. YX44 seems to produce a number of novel antibiotics with high pH stability and good solubility that have significant activity against S. aureus, including multidrug-resistant strains. Full article
(This article belongs to the Special Issue Natural Products from Streptomyces)
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13 pages, 4119 KiB  
Article
Elicitation of Antimicrobial Active Compounds by Streptomyces-Fungus Co-Cultures
by Matthieu Nicault, Ali Zaiter, Stéphane Dumarcay, Patrick Chaimbault, Eric Gelhaye, Pierre Leblond and Cyril Bontemps
Microorganisms 2021, 9(1), 178; https://doi.org/10.3390/microorganisms9010178 - 15 Jan 2021
Cited by 16 | Viewed by 4355
Abstract
The bacteria of the genus Streptomyces and Basidiomycete fungi harbor many biosynthetic gene clusters (BGCs) that are at the origin of many bioactive molecules with medical or industrial interests. Nevertheless, most BGCs do not express in standard lab growth conditions, preventing the full [...] Read more.
The bacteria of the genus Streptomyces and Basidiomycete fungi harbor many biosynthetic gene clusters (BGCs) that are at the origin of many bioactive molecules with medical or industrial interests. Nevertheless, most BGCs do not express in standard lab growth conditions, preventing the full metabolic potential of these organisms from being exploited. Because it generates biotic cues encountered during natural growth conditions, co-culture is a means to elicit such cryptic compounds. In this study, we explored 72 different Streptomyces-fungus interaction zones (SFIZs) generated during the co-culture of eight Streptomyces and nine fungi. Two SFIZs were selected because they showed an elicitation of anti-bacterial activity compared to mono-cultures. The study of these SFIZs showed that co-culture had a strong impact on the metabolic expression of each partner and enabled the expression of specific compounds. These results show that mimicking the biotic interactions present in this ecological niche is a promising avenue of research to explore the metabolic capacities of Streptomyces and fungi. Full article
(This article belongs to the Special Issue Natural Products from Streptomyces)
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11 pages, 993 KiB  
Article
Dudomycins: New Secondary Metabolites Produced after Heterologous Expression of an Nrps Cluster from Streptomyces albus ssp. Chlorinus Nrrl B-24108
by Constanze Lasch, Marc Stierhof, Marta Rodríguez Estévez, Maksym Myronovskyi, Josef Zapp and Andriy Luzhetskyy
Microorganisms 2020, 8(11), 1800; https://doi.org/10.3390/microorganisms8111800 - 16 Nov 2020
Cited by 6 | Viewed by 2616
Abstract
Since the 1950s, natural products of bacterial origin were systematically developed to be used as drugs with a wide range of medical applications. The available treatment options for many diseases are still not satisfying, wherefore, the discovery of new structures has not lost [...] Read more.
Since the 1950s, natural products of bacterial origin were systematically developed to be used as drugs with a wide range of medical applications. The available treatment options for many diseases are still not satisfying, wherefore, the discovery of new structures has not lost any of its importance. Beyond the great variety of already isolated and characterized metabolites, Streptomycetes still harbor uninvestigated gene clusters whose products can be accessed using heterologous expression in host organisms. This works presents the discovery of a set of structurally novel secondary metabolites, dudomycins A to D, through the expression of a cryptic NRPS cluster from Streptomyces albus ssp. Chlorinus NRRL B-24108 in the heterologous host strain Streptomyces albus Del14. A minimal set of genes, required for the production of dudomycins, was defined through gene inactivation experiments. This paper also proposes a model for dudomycin biosynthesis. Full article
(This article belongs to the Special Issue Natural Products from Streptomyces)
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20 pages, 2590 KiB  
Article
Production of Plant-Associated Volatiles by Select Model and Industrially Important Streptomyces spp.
by Zhenlong Cheng, Sean McCann, Nicoletta Faraone, Jody-Ann Clarke, E. Abbie Hudson, Kevin Cloonan, N. Kirk Hillier and Kapil Tahlan
Microorganisms 2020, 8(11), 1767; https://doi.org/10.3390/microorganisms8111767 - 11 Nov 2020
Cited by 11 | Viewed by 4630
Abstract
The Streptomyces produce a great diversity of specialized metabolites, including highly volatile compounds with potential biological activities. Volatile organic compounds (VOCs) produced by nine Streptomyces spp., some of which are of industrial importance, were collected and identified using gas chromatography–mass spectrometry (GC-MS). Biosynthetic [...] Read more.
The Streptomyces produce a great diversity of specialized metabolites, including highly volatile compounds with potential biological activities. Volatile organic compounds (VOCs) produced by nine Streptomyces spp., some of which are of industrial importance, were collected and identified using gas chromatography–mass spectrometry (GC-MS). Biosynthetic gene clusters (BGCs) present in the genomes of the respective Streptomyces spp. were also predicted to match them with the VOCs detected. Overall, 33 specific VOCs were identified, of which the production of 16 has not been previously reported in the Streptomyces. Among chemical classes, the most abundant VOCs were terpenes, which is consistent with predicted biosynthetic capabilities. In addition, 27 of the identified VOCs were plant-associated, demonstrating that some Streptomyces spp. can also produce such molecules. It is possible that some of the VOCs detected in the current study have roles in the interaction of Streptomyces with plants and other higher organisms, which might provide opportunities for their application in agriculture or industry. Full article
(This article belongs to the Special Issue Natural Products from Streptomyces)
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13 pages, 713 KiB  
Article
Streptomyces lydicamycinicus sp. nov. and Its Secondary Metabolite Biosynthetic Gene Clusters for Polyketide and Nonribosomal Peptide Compounds
by Hisayuki Komaki, Akira Hosoyama, Yasuhiro Igarashi and Tomohiko Tamura
Microorganisms 2020, 8(3), 370; https://doi.org/10.3390/microorganisms8030370 - 6 Mar 2020
Cited by 12 | Viewed by 4063
Abstract
(1) Background: Streptomyces sp. TP-A0598 derived from seawater produces lydicamycin and its congeners. We aimed to investigate its taxonomic status; (2) Methods: A polyphasic approach and whole genome analysis are employed; (3) Results: Strain TP-A0598 contained ll-diaminopimelic acid, glutamic acid, glycine, and [...] Read more.
(1) Background: Streptomyces sp. TP-A0598 derived from seawater produces lydicamycin and its congeners. We aimed to investigate its taxonomic status; (2) Methods: A polyphasic approach and whole genome analysis are employed; (3) Results: Strain TP-A0598 contained ll-diaminopimelic acid, glutamic acid, glycine, and alanine in its peptidoglycan. The predominant menaquinones were MK-9(H6) and MK-9(H8), and the major fatty acids were C16:0, iso-C15:0, iso-C16:0, and anteiso-C15:0. Streptomyces sp. TP-A0598 showed a 16S rDNA sequence similarity value of 99.93% (1 nucleottide difference) to Streptomyces angustmyceticus NRRL B-2347T. The digital DNA–DNA hybridisation value between Streptomyces sp. TP-A0598 and its closely related type strains was 25%–46%. Differences in phenotypic characteristics between Streptomyces sp. TP-A0598 and its phylogenetically closest relative, S. angustmyceticus NBRC 3934T, suggested strain TP-A0598 to be a novel species. Streptomyces sp. TP-A0598 and S. angustmyceticus NBRC 3934T harboured nine and 13 biosynthetic gene clusters for polyketides and nonribosomal peptides, respectively, among which only five clusters were shared between them, whereas the others are specific for each strain; and (4) Conclusions: For strain TP-A0598, the name Streptomyces lydicamycinicus sp. nov. is proposed; the type strain is TP-A0598T (=NBRC 110027T). Full article
(This article belongs to the Special Issue Natural Products from Streptomyces)
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Review

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18 pages, 1582 KiB  
Review
Recent Advances in Strategies for Activation and Discovery/Characterization of Cryptic Biosynthetic Gene Clusters in Streptomyces
by Chung Thanh Nguyen, Dipesh Dhakal, Van Thuy Thi Pham, Hue Thi Nguyen and Jae-Kyung Sohng
Microorganisms 2020, 8(4), 616; https://doi.org/10.3390/microorganisms8040616 - 24 Apr 2020
Cited by 47 | Viewed by 6939
Abstract
Streptomyces spp. are prolific sources of valuable natural products (NPs) that are of great interest in pharmaceutical industries such as antibiotics, anticancer chemotherapeutics, immunosuppressants, etc. Approximately two-thirds of all known antibiotics are produced by actinomycetes, most predominantly by Streptomyces. Nevertheless, in recent [...] Read more.
Streptomyces spp. are prolific sources of valuable natural products (NPs) that are of great interest in pharmaceutical industries such as antibiotics, anticancer chemotherapeutics, immunosuppressants, etc. Approximately two-thirds of all known antibiotics are produced by actinomycetes, most predominantly by Streptomyces. Nevertheless, in recent years, the chances of the discovery of novel and bioactive compounds from Streptomyces have significantly declined. The major hindrance for obtaining such bioactive compounds from Streptomyces is that most of the compounds are not produced in significant titers, or the biosynthetic gene clusters (BGCs) are cryptic. The rapid development of genome sequencing has provided access to a tremendous number of NP-BGCs embedded in the microbial genomes. In addition, the studies of metabolomics provide a portfolio of entire metabolites produced from the strain of interest. Therefore, through the integrated approaches of different-omics techniques, the connection between gene expression and metabolism can be established. Hence, in this review we summarized recent advancements in strategies for activating cryptic BGCs in Streptomyces by utilizing diverse state-of-the-art techniques. Full article
(This article belongs to the Special Issue Natural Products from Streptomyces)
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