New Phocoenamicin and Maklamicin Analogues from Cultures of Three Marine-Derived <i>Micromonospora</i> Strains
Antimicrobial resistance can be considered a hidden global pandemic and research must be reinforced for the discovery of new antibiotics. The spirotetronate class of polyketides, with more than 100 bioactive compounds described to date, has recently grown with the discovery of phocoenamicins, compou...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-08-01
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| Series: | Marine Drugs |
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| Online Access: | https://www.mdpi.com/1660-3397/21/8/443 |
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| author | Maria Kokkini Daniel Oves-Costales Pilar Sánchez Ángeles Melguizo Thomas A. Mackenzie Mercedes Pérez-Bonilla Jesús Martín Arianna Giusti Peter de Witte Francisca Vicente Olga Genilloud Fernando Reyes |
| author_facet | Maria Kokkini Daniel Oves-Costales Pilar Sánchez Ángeles Melguizo Thomas A. Mackenzie Mercedes Pérez-Bonilla Jesús Martín Arianna Giusti Peter de Witte Francisca Vicente Olga Genilloud Fernando Reyes |
| author_sort | Maria Kokkini |
| collection | DOAJ |
| description | Antimicrobial resistance can be considered a hidden global pandemic and research must be reinforced for the discovery of new antibiotics. The spirotetronate class of polyketides, with more than 100 bioactive compounds described to date, has recently grown with the discovery of phocoenamicins, compounds displaying different antibiotic activities. Three marine <i>Micromonospora</i> strains (CA-214671, CA-214658 and CA-218877), identified as phocoenamicins producers, were chosen to scale up their production and LC/HRMS analyses proved that EtOAc extracts from their culture broths produce several structurally related compounds not disclosed before. Herein, we report the production, isolation and structural elucidation of two new phocoenamicins, phocoenamicins D and E (<b>1</b>–<b>2</b>), along with the known phocoenamicin, phocoenamicins B and C (<b>3</b>–<b>5</b>), as well as maklamicin (<b>7</b>) and maklamicin B (<b>6</b>), the latter being reported for the first time as a natural product. All the isolated compounds were tested against various human pathogens and revealed diverse strong to negligible activity against methicillin-resistant <i>Staphylococcus aureus</i>, <i>Mycobacterium tuberculosis</i> H37Ra, <i>Enterococcus faecium</i> and <i>Enterococcus faecalis</i>. Their cell viability was also evaluated against the human liver adenocarcinoma cell line (Hep G2), demonstrating weak or no cytotoxicity. Lastly, the safety of the major compounds obtained, phocoenamicin (<b>3</b>), phocoenamicin B (<b>4</b>) and maklamicin (<b>7</b>), was tested against zebrafish eleuthero embryos and all of them displayed no toxicity up to a concentration of 25 μM. |
| first_indexed | 2024-03-10T23:46:15Z |
| format | Article |
| id | doaj.art-25ec2d2a470f457cb2fcf2e150e17006 |
| institution | Directory Open Access Journal |
| issn | 1660-3397 |
| language | English |
| last_indexed | 2024-03-10T23:46:15Z |
| publishDate | 2023-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Marine Drugs |
| spelling | doaj.art-25ec2d2a470f457cb2fcf2e150e170062023-11-19T01:58:08ZengMDPI AGMarine Drugs1660-33972023-08-0121844310.3390/md21080443New Phocoenamicin and Maklamicin Analogues from Cultures of Three Marine-Derived <i>Micromonospora</i> StrainsMaria Kokkini0Daniel Oves-Costales1Pilar Sánchez2Ángeles Melguizo3Thomas A. Mackenzie4Mercedes Pérez-Bonilla5Jesús Martín6Arianna Giusti7Peter de Witte8Francisca Vicente9Olga Genilloud10Fernando Reyes11Fundación MEDINA, Centro de Excelencia en Investigación de Medicamentos Innovadores en Andalucía, Parque Tecnológico Ciencias de la Salud, Avda. del Conocimiento 34, Armilla, 18016 Granada, SpainFundación MEDINA, Centro de Excelencia en Investigación de Medicamentos Innovadores en Andalucía, Parque Tecnológico Ciencias de la Salud, Avda. del Conocimiento 34, Armilla, 18016 Granada, SpainFundación MEDINA, Centro de Excelencia en Investigación de Medicamentos Innovadores en Andalucía, Parque Tecnológico Ciencias de la Salud, Avda. del Conocimiento 34, Armilla, 18016 Granada, SpainFundación MEDINA, Centro de Excelencia en Investigación de Medicamentos Innovadores en Andalucía, Parque Tecnológico Ciencias de la Salud, Avda. del Conocimiento 34, Armilla, 18016 Granada, SpainFundación MEDINA, Centro de Excelencia en Investigación de Medicamentos Innovadores en Andalucía, Parque Tecnológico Ciencias de la Salud, Avda. del Conocimiento 34, Armilla, 18016 Granada, SpainFundación MEDINA, Centro de Excelencia en Investigación de Medicamentos Innovadores en Andalucía, Parque Tecnológico Ciencias de la Salud, Avda. del Conocimiento 34, Armilla, 18016 Granada, SpainFundación MEDINA, Centro de Excelencia en Investigación de Medicamentos Innovadores en Andalucía, Parque Tecnológico Ciencias de la Salud, Avda. del Conocimiento 34, Armilla, 18016 Granada, SpainLaboratory for Molecular Biodiscovery, Department of Pharmaceutical and Pharmacological Sciences, University of Leuven, O & N II Herestraat 49-box 824, 3000 Leuven, BelgiumLaboratory for Molecular Biodiscovery, Department of Pharmaceutical and Pharmacological Sciences, University of Leuven, O & N II Herestraat 49-box 824, 3000 Leuven, BelgiumFundación MEDINA, Centro de Excelencia en Investigación de Medicamentos Innovadores en Andalucía, Parque Tecnológico Ciencias de la Salud, Avda. del Conocimiento 34, Armilla, 18016 Granada, SpainFundación MEDINA, Centro de Excelencia en Investigación de Medicamentos Innovadores en Andalucía, Parque Tecnológico Ciencias de la Salud, Avda. del Conocimiento 34, Armilla, 18016 Granada, SpainFundación MEDINA, Centro de Excelencia en Investigación de Medicamentos Innovadores en Andalucía, Parque Tecnológico Ciencias de la Salud, Avda. del Conocimiento 34, Armilla, 18016 Granada, SpainAntimicrobial resistance can be considered a hidden global pandemic and research must be reinforced for the discovery of new antibiotics. The spirotetronate class of polyketides, with more than 100 bioactive compounds described to date, has recently grown with the discovery of phocoenamicins, compounds displaying different antibiotic activities. Three marine <i>Micromonospora</i> strains (CA-214671, CA-214658 and CA-218877), identified as phocoenamicins producers, were chosen to scale up their production and LC/HRMS analyses proved that EtOAc extracts from their culture broths produce several structurally related compounds not disclosed before. Herein, we report the production, isolation and structural elucidation of two new phocoenamicins, phocoenamicins D and E (<b>1</b>–<b>2</b>), along with the known phocoenamicin, phocoenamicins B and C (<b>3</b>–<b>5</b>), as well as maklamicin (<b>7</b>) and maklamicin B (<b>6</b>), the latter being reported for the first time as a natural product. All the isolated compounds were tested against various human pathogens and revealed diverse strong to negligible activity against methicillin-resistant <i>Staphylococcus aureus</i>, <i>Mycobacterium tuberculosis</i> H37Ra, <i>Enterococcus faecium</i> and <i>Enterococcus faecalis</i>. Their cell viability was also evaluated against the human liver adenocarcinoma cell line (Hep G2), demonstrating weak or no cytotoxicity. Lastly, the safety of the major compounds obtained, phocoenamicin (<b>3</b>), phocoenamicin B (<b>4</b>) and maklamicin (<b>7</b>), was tested against zebrafish eleuthero embryos and all of them displayed no toxicity up to a concentration of 25 μM.https://www.mdpi.com/1660-3397/21/8/443antimicrobial resistancedrug discoverynatural productsmarine actinomycetespolyketidesspirotetronates |
| spellingShingle | Maria Kokkini Daniel Oves-Costales Pilar Sánchez Ángeles Melguizo Thomas A. Mackenzie Mercedes Pérez-Bonilla Jesús Martín Arianna Giusti Peter de Witte Francisca Vicente Olga Genilloud Fernando Reyes New Phocoenamicin and Maklamicin Analogues from Cultures of Three Marine-Derived <i>Micromonospora</i> Strains Marine Drugs antimicrobial resistance drug discovery natural products marine actinomycetes polyketides spirotetronates |
| title | New Phocoenamicin and Maklamicin Analogues from Cultures of Three Marine-Derived <i>Micromonospora</i> Strains |
| title_full | New Phocoenamicin and Maklamicin Analogues from Cultures of Three Marine-Derived <i>Micromonospora</i> Strains |
| title_fullStr | New Phocoenamicin and Maklamicin Analogues from Cultures of Three Marine-Derived <i>Micromonospora</i> Strains |
| title_full_unstemmed | New Phocoenamicin and Maklamicin Analogues from Cultures of Three Marine-Derived <i>Micromonospora</i> Strains |
| title_short | New Phocoenamicin and Maklamicin Analogues from Cultures of Three Marine-Derived <i>Micromonospora</i> Strains |
| title_sort | new phocoenamicin and maklamicin analogues from cultures of three marine derived i micromonospora i strains |
| topic | antimicrobial resistance drug discovery natural products marine actinomycetes polyketides spirotetronates |
| url | https://www.mdpi.com/1660-3397/21/8/443 |
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