New myxobacteria of the Myxococcaceae clade produce angiolams with antiparasitic activities
ABSTRACTIn the past century, microbial natural products have proven themselves to be substantial and fruitful sources of anti-infectives. In addition to the well-studied Actinobacteria, understudied bacterial taxa like the Gram-negative myxobacteria have increasingly gained attention in the ongoing...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
American Society for Microbiology
2024-03-01
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| Series: | Microbiology Spectrum |
| Subjects: | |
| Online Access: | https://journals.asm.org/doi/10.1128/spectrum.03689-23 |
| _version_ | 1797276765675061248 |
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| author | Sebastian Walesch Ronald Garcia Abdelhalim B. Mahmoud Fabian Panter Sophie Bollenbach Pascal Mäser Marcel Kaiser Daniel Krug Rolf Müller |
| author_facet | Sebastian Walesch Ronald Garcia Abdelhalim B. Mahmoud Fabian Panter Sophie Bollenbach Pascal Mäser Marcel Kaiser Daniel Krug Rolf Müller |
| author_sort | Sebastian Walesch |
| collection | DOAJ |
| description | ABSTRACTIn the past century, microbial natural products have proven themselves to be substantial and fruitful sources of anti-infectives. In addition to the well-studied Actinobacteria, understudied bacterial taxa like the Gram-negative myxobacteria have increasingly gained attention in the ongoing search for novel and biologically active natural products. In the course of a regional sampling campaign to source novel myxobacteria, we recently uncovered new myxobacterial strains MCy12716 and MCy12733 belonging to the Myxococcaceae clade. Early bioactivity screens of the bacterial extracts revealed the presence of bioactive natural products that were identified as angiolam A and several novel derivatives. Sequencing of the corresponding producer strains allowed the identification of the angiolam biosynthetic gene cluster, which was verified by targeted gene inactivation. Based on bioinformatic analysis of the biosynthetic gene cluster, a concise biosynthesis model was devised to explain angiolam biosynthesis. Importantly, novel angiolam derivatives uncovered in this study named angiolams B, C, and D were found to display promising antiparasitic activities against the malaria pathogen Plasmodium falciparum in the 0.3–0.8 µM range.IMPORTANCEThe COVID-19 pandemic and continuously emerging antimicrobial resistance (AMR) have recently raised awareness about limited treatment options against infectious diseases. However, the shortage of treatment options against protozoal parasitic infections, like malaria, is much more severe, especially for the treatment of so-called neglected tropical diseases. The detection of anti-parasitic bioactivities of angiolams produced by MCy12716 and MCy12733 displays the hidden potential of scarcely studied natural products to have promising biological activities in understudied indications. Furthermore, the improved biological activities of novel angiolam derivatives against Plasmodium falciparum and the evaluation of its biosynthesis display the opportunities of the angiolam scaffold on route to treat protozoal parasitic infections as well as possible ways to increase the production of derivatives with improved bioactivities. |
| first_indexed | 2024-03-07T15:32:58Z |
| format | Article |
| id | doaj.art-b6e3d736a4d74369a8c28d3ceeea480d |
| institution | Directory Open Access Journal |
| issn | 2165-0497 |
| language | English |
| last_indexed | 2024-03-07T15:32:58Z |
| publishDate | 2024-03-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | Microbiology Spectrum |
| spelling | doaj.art-b6e3d736a4d74369a8c28d3ceeea480d2024-03-05T14:04:37ZengAmerican Society for MicrobiologyMicrobiology Spectrum2165-04972024-03-0112310.1128/spectrum.03689-23New myxobacteria of the Myxococcaceae clade produce angiolams with antiparasitic activitiesSebastian Walesch0Ronald Garcia1Abdelhalim B. Mahmoud2Fabian Panter3Sophie Bollenbach4Pascal Mäser5Marcel Kaiser6Daniel Krug7Rolf Müller8Helmholtz Centre for Infection Research, Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), Saarland University Campus, Saarbrücken, GermanyHelmholtz Centre for Infection Research, Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), Saarland University Campus, Saarbrücken, GermanyHelmholtz Centre for Infection Research, Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), Saarland University Campus, Saarbrücken, GermanyHelmholtz Centre for Infection Research, Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), Saarland University Campus, Saarbrücken, GermanyHelmholtz Centre for Infection Research, Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), Saarland University Campus, Saarbrücken, GermanyParasite Chemotherapy Unit, Swiss Tropical and Public Health Institute, Allschwil, SwitzerlandParasite Chemotherapy Unit, Swiss Tropical and Public Health Institute, Allschwil, SwitzerlandHelmholtz Centre for Infection Research, Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), Saarland University Campus, Saarbrücken, GermanyHelmholtz Centre for Infection Research, Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), Saarland University Campus, Saarbrücken, GermanyABSTRACTIn the past century, microbial natural products have proven themselves to be substantial and fruitful sources of anti-infectives. In addition to the well-studied Actinobacteria, understudied bacterial taxa like the Gram-negative myxobacteria have increasingly gained attention in the ongoing search for novel and biologically active natural products. In the course of a regional sampling campaign to source novel myxobacteria, we recently uncovered new myxobacterial strains MCy12716 and MCy12733 belonging to the Myxococcaceae clade. Early bioactivity screens of the bacterial extracts revealed the presence of bioactive natural products that were identified as angiolam A and several novel derivatives. Sequencing of the corresponding producer strains allowed the identification of the angiolam biosynthetic gene cluster, which was verified by targeted gene inactivation. Based on bioinformatic analysis of the biosynthetic gene cluster, a concise biosynthesis model was devised to explain angiolam biosynthesis. Importantly, novel angiolam derivatives uncovered in this study named angiolams B, C, and D were found to display promising antiparasitic activities against the malaria pathogen Plasmodium falciparum in the 0.3–0.8 µM range.IMPORTANCEThe COVID-19 pandemic and continuously emerging antimicrobial resistance (AMR) have recently raised awareness about limited treatment options against infectious diseases. However, the shortage of treatment options against protozoal parasitic infections, like malaria, is much more severe, especially for the treatment of so-called neglected tropical diseases. The detection of anti-parasitic bioactivities of angiolams produced by MCy12716 and MCy12733 displays the hidden potential of scarcely studied natural products to have promising biological activities in understudied indications. Furthermore, the improved biological activities of novel angiolam derivatives against Plasmodium falciparum and the evaluation of its biosynthesis display the opportunities of the angiolam scaffold on route to treat protozoal parasitic infections as well as possible ways to increase the production of derivatives with improved bioactivities.https://journals.asm.org/doi/10.1128/spectrum.03689-23natural productsmyxobacteriadrug discoveryanti-parasiticstructure elucidationbiosynthesis |
| spellingShingle | Sebastian Walesch Ronald Garcia Abdelhalim B. Mahmoud Fabian Panter Sophie Bollenbach Pascal Mäser Marcel Kaiser Daniel Krug Rolf Müller New myxobacteria of the Myxococcaceae clade produce angiolams with antiparasitic activities Microbiology Spectrum natural products myxobacteria drug discovery anti-parasitic structure elucidation biosynthesis |
| title | New myxobacteria of the Myxococcaceae clade produce angiolams with antiparasitic activities |
| title_full | New myxobacteria of the Myxococcaceae clade produce angiolams with antiparasitic activities |
| title_fullStr | New myxobacteria of the Myxococcaceae clade produce angiolams with antiparasitic activities |
| title_full_unstemmed | New myxobacteria of the Myxococcaceae clade produce angiolams with antiparasitic activities |
| title_short | New myxobacteria of the Myxococcaceae clade produce angiolams with antiparasitic activities |
| title_sort | new myxobacteria of the myxococcaceae clade produce angiolams with antiparasitic activities |
| topic | natural products myxobacteria drug discovery anti-parasitic structure elucidation biosynthesis |
| url | https://journals.asm.org/doi/10.1128/spectrum.03689-23 |
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