Genome‐Based Identification of a Plant‐Associated Marine Bacterium as a Rich Natural Product Source

Ueoka, Ryoko; Bhushan, Agneya; Probst, Silke I.; Bray, Walter M.; Lokey, R. Scott; Linington, Roger G.; Piel, Jörn

doi:10.1002/ange.201805673

Cited by 10 publications

(3 citation statements)

References 46 publications

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“…Recently, there has been great interest in natural products from unexplored microbial sources, especially actinomycetes [38], marine ecosystems [39], and microorganisms associated with plants [40], mammals [41], and invertebrates [42] from marine and terrestrial habitats. Despite the most important antibiotics currently in use being derived from cultivable microorganisms, only a tiny fraction of microorganisms can be cultivated in routine lab cultures [43].…”

Section: Microbial Sources In Drug Discoverymentioning

confidence: 99%

Microbial Natural Products in Drug Discovery

et al. 2020

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Over a long period of time, humans have explored many natural resources looking for remedies of various ailments. Traditional medicines have played an intrinsic role in human life for thousands of years, with people depending on medicinal plants and their products as dietary supplements as well as using them therapeutically for treatment of chronic disorders, such as cancer, malaria, diabetes, arthritis, inflammation, and liver and cardiac disorders. However, plant resources are not sufficient for treatment of recently emerging diseases. In addition, the seasonal availability and other political factors put constrains on some rare plant species. The actual breakthrough in drug discovery came concurrently with the discovery of penicillin from Penicillium notatum in 1929. This discovery dramatically changed the research of natural products and positioned microbial natural products as one of the most important clues in drug discovery due to availability, variability, great biodiversity, unique structures, and the bioactivities produced. The number of commercially available therapeutically active compounds from microbial sources to date exceeds those discovered from other sources. In this review, we introduce a short history of microbial drug discovery as well as certain features and recent research approaches, specifying the microbial origin, their featured molecules, and the diversity of the producing species. Moreover, we discuss some bioactivities as well as new approaches and trends in research in this field.

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Section: Microbial Sources In Drug Discoverymentioning

confidence: 99%

Microbial Natural Products in Drug Discovery

et al. 2020

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“…1). The polyyne Sch 31828 isolated from the Actinobacteria phylum [10], and fischerellins A and B from the Cyanobacteria phylum [11,12], both of their associated gene cluster remain unknown. While alkyne [13] and polyyne [6] biosynthetic mechanisms have been .…”

Section: Mainmentioning

confidence: 99%

Exploration of polyyne biosynthetic gene cluster diversity in bacteria leads to the discovery of thePseudomonaspolyyne protegencin

Mullins¹,

Webster²,

Kim

et al. 2021

Preprint

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Natural products that possess alkyne or polyyne moieties have been isolated from a variety of biological sources. In bacteria their biosynthesis has been defined, however, the distribution of polyyne biosynthetic gene clusters (BGCs), and their evolutionary relationship to alkyne biosynthesis, have not been addressed. We explored the distribution of alkyne biosynthesis gene cassettes throughout bacteria, revealing evidence of multiple horizontal gene transfer events. Investigating the evolutionary connection between alkyne and polyyne biosynthesis identified a monophyletic clade possessing a conserved seven-gene cassette for polyyne biosynthesis. Mapping the diversity of these conserved genes revealed a phylogenetic clade representing a polyyne BGC in Pseudomonas, pgn, and subsequent pathway mutagenesis and analytical chemistry characterised the associated metabolite, protegencin. In addition to unifying and expanding our knowledge of polyyne diversity, our results show that alkyne and polyyne biosynthetic gene clusters are promiscuous within bacteria. Systematic mapping of conserved biosynthetic genes across bacterial genomic diversity has proven to be a successful method for discovering natural products.

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“…Consequently, PTMs embody a relatively scarce example of an antibiotic family produced by both Gram-positive and Gram-negative organisms (3,4). Over time, reports of PTM molecules and their encoding BGCs expanded beyond Streptomyces and Lysobacter to include several other filamentous actinomycetes (Kitasatospora, Salinispora, Micromonospora, Saccharopolyspora, Saccharothrix, Umezawaea, Nocardiopsis, Actinokineospora, and Actinoalloteichus), gamma-proteobacteria (Pseudoalteromonas, Colwellia, Gynuella, and Saccharophagus), as well as the firmicute Pelosinus fermentans (1,2,(5)(6)(7)(8)(9)(10)(11)(12)(13)(14).…”

Section: Introductionmentioning

confidence: 99%

Critical analysis of polycyclic tetramate macrolactam biosynthetic cluster phylogeny and functional diversity

Harper,

Day,

Tsingos

et al. 2024

Preprint

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Polycyclic tetramate macrolactams (PTMs) are bioactive natural products commonly associated with certain actinobacterial and proteobacterial lineages. These molecules have been the subject of numerous structure-activity investigations since the 1970s. New members continue to be pursued in wild and engineered bacterial strains, and advances in PTM biosynthesis suggests their outwardly simplistic biosynthetic gene clusters (BGCs) belie unexpected product complexity. Towards addressing the origins of this complexity and understanding its influence on PTM discovery, we engaged in a combination of bioinformatics to systematically classify PTM BGCs, and PTM- targeted metabolomics to compare the products of select BGC types. By comparing groups of producers and BGC mutants, we exposed knowledge gaps that complicate bioinformatics-driven product predictions. In sum, we provide new insights into the evolution of PTM BGCs while systematically accounting for the PTMs discovered thus far. The combined computational and metabologenomic findings presented here should prove useful for guiding future discovery.

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Genome‐Based Identification of a Plant‐Associated Marine Bacterium as a Rich Natural Product Source

Abstract: Supportinginformation and the ORCID identification number(s) for the author(s) of this article can be found under: https://doi.

Cited by 10 publications

References 46 publications

Microbial Natural Products in Drug Discovery

Microbial Natural Products in Drug Discovery

Exploration of polyyne biosynthetic gene cluster diversity in bacteria leads to the discovery of thePseudomonaspolyyne protegencin

Critical analysis of polycyclic tetramate macrolactam biosynthetic cluster phylogeny and functional diversity

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