New Microbial Sources of Natural Products: Their Biology, Chemistry and Biosynthetic Machinery

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

Deadline for manuscript submissions: closed (31 May 2023) | Viewed by 11629

Special Issue Editors


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Guest Editor
Helmholtz-Institute for Pharmaceutical Research Saarland (HIPS), Saarbrücken, Germany
Interests: mass spectrometry of natural products; myxobacteria; biosynthetic pathways; genome- and metabolome mining
Special Issues, Collections and Topics in MDPI journals

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Guest Editor
Microbial Natural Product (MINS) Department, Helmholtz Institute for Pharmaceutical Research Saarland (HIPS); German Centre for Infection Research (DZIF), Partner Site Hannover-Braunschweig, Braunschweig, Germany
Interests: microorganisms; myxobacteria; microbial natural products; drug discovery; phylogeny; taxonomy; systematics; metagenomics; genomics
Special Issues, Collections and Topics in MDPI journals

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Guest Editor
Department of Chemistry, Scripps Research, Florida Campus, 130 Scripps Way, Jupiter, FL 33458, USA
Interests: natural products discovery; mass spectrometry; structure elucidation; metabolomics; supercritical fluid chromatography; soil bacteria; bioassays

Special Issue Information

Dear Colleagues,

This Special Issue is devoted to microorganisms as producers of natural products. Furthermore, termed “specialized metabolites”, these compounds made by bacteria or fungi have a strong track record as valuable lead structures for drug discovery in areas including cancer therapy, the fight against infectious diseases and agriculture. 

Contributions should feature a combination of methods, which could range from basic microbiology for novel strain discovery to chemical analytics for structure elucidation to molecular biology methods. These could be aimed at connecting molecules to biosynthetic genes, revealing specific enzymatic steps during biosynthesis, enabling production improvement, or gaining insights into bioactivity, host self-resistance, and the biological function of specialized metabolites. 

Moreover, we intend to highlight recent studies where genomics-, transcriptomics- or metabolomics-based approaches were instrumental for characterizing new producers of natural products. We welcome in particular reports of novel microbial taxa using such methods to uncover new specialized metabolites and connect them to the underlying biosynthetic pathways. Studies where innovative methods themselves are the main focus, such as biotechnological, analytical or bioinformatic techniques supporting microbial strain- or compound characterization, are also within the scope of this Special Issue.

Dr. Daniel Krug
Dr. Ronald O. Garcia
Dr. Chantal Bader
Guest Editors

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Published Papers (5 papers)

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Research

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8 pages, 976 KiB  
Article
Flavacol and Its Novel Derivative 3-β-Hydroxy Flavacol from Streptomyces sp. Pv 4-95 after the Expression of Heterologous AdpA
by Stepan Tistechok, Marc Stierhof, Anna Kachor, Maksym Myronovskyi, Oleksandr Gromyko and Andriy Luzhetskyy
Microorganisms 2022, 10(12), 2335; https://doi.org/10.3390/microorganisms10122335 - 25 Nov 2022
Cited by 2 | Viewed by 1270
Abstract
Actinomycetes are one of the main producers of biologically active compounds. However, their capabilities have not been fully evaluated due to the presence of many unexpressed silent clusters; moreover, actinomycetes can probably produce new or previously discovered natural products under certain conditions. Overexpressing [...] Read more.
Actinomycetes are one of the main producers of biologically active compounds. However, their capabilities have not been fully evaluated due to the presence of many unexpressed silent clusters; moreover, actinomycetes can probably produce new or previously discovered natural products under certain conditions. Overexpressing the adpA gene into streptomycetes strains can unlock silent biosynthetic gene clusters. Herein, we showed that by applying this approach to Streptomyces sp. Pv 4-95 isolated from Phyllostachys viridiglaucescens rhizosphere soil, two new mass peaks were identified. NMR structure analysis identified these compounds as flavacol and a new 3-β-hydroxy flavacol derivative. We suggest that the presence of heterologous AdpA has no direct effect on the synthesis of flavacol and its derivatives in the Pv 4-95 strain. However, AdpA affects the synthesis of precursors by increasing their quantity, which then condenses into the resulting compounds. Full article
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17 pages, 2744 KiB  
Article
Discovery, Biosynthesis and Biological Activity of a Succinylated Myxochelin from the Myxobacterial Strain MSr12020
by Dorothy A. Okoth, Joachim J. Hug, Ronald Garcia and Rolf Müller
Microorganisms 2022, 10(10), 1959; https://doi.org/10.3390/microorganisms10101959 - 30 Sep 2022
Cited by 3 | Viewed by 1839
Abstract
Myxobacteria feature unique biological characteristics, including their capability to glide on the surface, undergo different multicellular developmental stages and produce structurally unique natural products such as the catecholate-type siderophores myxochelins A and B. Herein, we report the isolation, structure elucidation and a proposed [...] Read more.
Myxobacteria feature unique biological characteristics, including their capability to glide on the surface, undergo different multicellular developmental stages and produce structurally unique natural products such as the catecholate-type siderophores myxochelins A and B. Herein, we report the isolation, structure elucidation and a proposed biosynthesis of the new congener myxochelin B-succinate from the terrestrial myxobacterial strain MSr12020, featuring a succinyl decoration at its primary amine group. Myxochelin-B-succinate exhibited antibacterial growth inhibition and moderate cytotoxic activity against selected human cancer cell lines. This unique chemical modification of myxochelin B might provide interesting insights for future microbiological studies to understand the biological function and biosynthesis of secondary metabolite succinylation. Full article
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17 pages, 2713 KiB  
Article
Corallococcus soli sp. Nov., a Soil Myxobacterium Isolated from Subtropical Climate, Chalus County, Iran, and Its Potential to Produce Secondary Metabolites
by Zahra Khosravi Babadi, Ronald Garcia, Gholam Hossein Ebrahimipour, Chandra Risdian, Peter Kämpfer, Michael Jarek, Rolf Müller and Joachim Wink
Microorganisms 2022, 10(7), 1262; https://doi.org/10.3390/microorganisms10071262 - 21 Jun 2022
Cited by 6 | Viewed by 2210
Abstract
A novel myxobacterial strain ZKHCc1 1396T was isolated in 2017 from a soil sample collected along Chalus Road connecting Tehran and Mazandaran, Iran. It was a Gram-negative, rod-shaped bacterial strain that displayed the general features of Corallococcus, including gliding and fruiting body [...] Read more.
A novel myxobacterial strain ZKHCc1 1396T was isolated in 2017 from a soil sample collected along Chalus Road connecting Tehran and Mazandaran, Iran. It was a Gram-negative, rod-shaped bacterial strain that displayed the general features of Corallococcus, including gliding and fruiting body formation on agar and microbial lytic activity. Strain ZKHCc1 1396T was characterized as an aerobic, mesophilic, and chemoheterotrophic bacterium resistant to many antibiotics. The major cellular fatty acids were branched-chain iso-C17:0 2-OH, iso-C15:0, iso-C17:1, and iso-C17:0. The strain showed the highest 16S rRNA gene sequence similarity to Corallococcusterminator CA054AT (99.67%) and C. praedator CA031BT (99.17%), and formed a novel branch both in the 16S rRNA gene sequence and phylogenomic tree. The genome size was 9,437,609 bp, with a DNA G + C content of 69.8 mol%. The strain had an average nucleotide identity (ANI) value lower than the species cut-off (95%), and with the digital DNA–DNA hybridization (dDDH) below the 70% threshold compared to the closest type strains. Secondary metabolite and biosynthetic gene cluster analyses revealed the strain’s potential to produce novel compounds. Based on polyphasic taxonomic characterization, we propose that strain ZKHCc1 1396T represents a novel species, Corallococcus soli sp. nov. (NCCB 100659T = CIP 111634T). Full article
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13 pages, 2720 KiB  
Article
Myxobacteria of the Cystobacterineae Suborder Are Producers of New Vitamin K2 Derived Myxoquinones
by Fabian Panter, Alexander Popoff, Ronald Garcia, Daniel Krug and Rolf Müller
Microorganisms 2022, 10(3), 534; https://doi.org/10.3390/microorganisms10030534 - 28 Feb 2022
Cited by 2 | Viewed by 2647
Abstract
Vitamin K is an essential, lipid soluble vitamin that plays an important role in the human blood coagulation cascade as well as in the life cycle of bacteria and plants. In this study, we report the isolation and structure elucidation of unprecedented polyhydroxylated [...] Read more.
Vitamin K is an essential, lipid soluble vitamin that plays an important role in the human blood coagulation cascade as well as in the life cycle of bacteria and plants. In this study, we report the isolation and structure elucidation of unprecedented polyhydroxylated menaquinone variants named myxoquinones that are produced by myxobacteria and structurally belong to the Vitamin K family. We analyze the occurrence of myxoquinones across an LC-MS data collection from myxobacterial extracts and shed light on the distribution of myxoquinone-type biosynthetic gene clusters among publicly available myxobacterial genomes. Our findings indicate that myxoquinones are specifically produced by strains of the Cystobacterineae suborder within myxobacteria. Furthermore, bioinformatic analysis of the matching gene clusters allowed us to propose a biosynthetic model for myxoquinone formation. Due to their increased water-solubility, the myxoquinones could be a suitable starting point for the development of a better bioavailable treatment of vitamin K deficiency. Full article
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Review

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22 pages, 1351 KiB  
Review
Exploring the Promise of Endophytic Fungi: A Review of Novel Antimicrobial Compounds
by Daniel J. Caruso, Enzo A. Palombo, Simon E. Moulton and Bita Zaferanloo
Microorganisms 2022, 10(10), 1990; https://doi.org/10.3390/microorganisms10101990 - 08 Oct 2022
Cited by 29 | Viewed by 2584
Abstract
Over the last few decades, many of the existing drugs used to treat infectious diseases have become increasingly ineffective due to the global emergence of antimicrobial resistance (AMR). As such, there is a constant demand to find new, effective compounds that could help [...] Read more.
Over the last few decades, many of the existing drugs used to treat infectious diseases have become increasingly ineffective due to the global emergence of antimicrobial resistance (AMR). As such, there is a constant demand to find new, effective compounds that could help to alleviate some of this pressure. Endophytic fungi have captured the attention of many researchers in this field, as they have displayed a vast ability to produce novel bioactive compounds, many of which possess wide-ranging antimicrobial activities. However, while highly promising, research in this area is still in its infancy. Endophytes inhabit the healthy tissues of plants asymptomatically, resulting in a mutualistic symbiosis in which the endophytes produce a plethora of bioactive compounds that support the fitness of the host plant. These compounds display great chemical diversity, representing structural groups, such as aliphatic compounds, alkaloids, peptides, phenolics, polyketides and terpenoids. In this review, the significant antimicrobial potential of endophytic fungi is detailed, highlighting their ability to produce novel and diverse antimicrobial compounds active against human, plant and marine pathogens. In doing so, it also highlights the significant contributions that endophytic fungi can make in our battle against AMR, thus providing the motivation to increase efforts in the search for new and effective antimicrobial drugs. Full article
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