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From a Natural Product to Its Biosynthetic Gene Cluster: A Demonstration Using Polyketomycin from Streptomyces diastatochromogenes Tü6028
Published on: January 13, 2017
Polyenic Antibiotics and Other Antifungal Compounds Produced by Hemolytic Streptomyces Species
Jan Bobek1,2, Eliška Filipová1, Natalie Bergman2
1Institute of Immunology and Microbiology, 1st Faculty of Medicine, Charles University, Studničkova 7, 128 00 Prague, Czech Republic.
Abstract:
Streptomyces are of great interest in the pharmaceutical industry as they produce a plethora of secondary metabolites that act as antibacterial and antifungal agents. They may thrive on their own in the soil, or associate with other organisms, such as plants or invertebrates. Some soil-derived strains exhibit hemolytic properties when cultivated on blood agar, raising the question of whether hemolysis could be a virulence factor of the bacteria. In this work we examined hemolytic compound production in 23 β-hemolytic Streptomyces isolates; of these 12 were soil-derived, 10 were arthropod-associated, and 1 was plant-associated. An additional human-associated S. sp. TR1341 served as a control. Mass spectrometry analysis suggested synthesis of polyene molecules responsible for the hemolysis: candicidins, filipins, strevertene A, tetrafungin, and tetrin A, as well as four novel polyene compounds (denoted here as polyene A, B, C, and D) in individual liquid cultures or paired co-cultures. The non-polyene antifungal compounds actiphenol and surugamide A were also identified. The findings indicate that the ability of Streptomyces to produce cytolytic compounds (here manifested by hemolysis on blood agar) is an intrinsic feature of the bacteria in the soil environment and could even serve as a virulence factor when colonizing available host organisms. Additionally, a literature review of polyenes and non-polyene hemolytic metabolites produced by Streptomyces is presented.
Insights
Streptomyces bacteria produce hemolytic compounds, including novel polyenes, which may act as virulence factors. Their ability to produce cytolytic substances is intrinsic to their soil existence.
Area of Science:
- Microbiology and Biochemistry
- Natural Product Chemistry
Background:
- Streptomyces are vital pharmaceutical sources for antibacterial and antifungal compounds.
- Hemolytic properties in some Streptomyces strains suggest potential virulence factors.
- Understanding the cytolytic mechanisms of Streptomyces is crucial for pharmaceutical applications.
Approach:
- Analyzed 23 β-hemolytic Streptomyces isolates from diverse environments (soil, arthropod, plant, human).
- Utilized mass spectrometry to identify hemolytic polyene and non-polyene compounds.
- Investigated compound production in individual and co-cultures.
Key Points:
- Identified known polyenes (candicidins, filipins, etc.) and four novel polyenes (A-D) responsible for hemolysis.
- Detected non-polyene antifungal compounds actiphenol and surugamide A.
- Confirmed hemolysis as an intrinsic trait of soil-derived Streptomyces.
Conclusions:
- Streptomyces possess an inherent capacity for producing cytolytic compounds.
- Hemolysis can function as a virulence factor during host organism colonization.
- This study expands the known repertoire of hemolytic metabolites from Streptomyces.
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