Exploring Micromonospora as Phocoenamicins Producers

• Published in: Marine drugs Vol. 20; no. 12; p. 769
• Main Authors: Kokkini, Maria, González Heredia, Cristina, Oves-Costales, Daniel, de la Cruz, Mercedes, Sánchez, Pilar, Martín, Jesús, Vicente, Francisca, Genilloud, Olga, Reyes, Fernando
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 07.12.2022; MDPI
• Subjects: Actinobacteria - genetics; actinomycetes; Anti-Bacterial Agents - chemistry; Antibiotics; Antimicrobial agents; antimicrobial resistance; Biological activity; Culture media; drug discovery; Drug resistance; Fermentation; Gram-positive bacteria; High-throughput screening; Identification; Laboratories; Marine environment; Metabolism; Metabolites; Metabolomics; Methicillin; Methicillin-Resistant Staphylococcus aureus; Micromonospora; Micromonospora - chemistry; Microorganisms; Molecular Structure; Natural products; polyketides; rRNA 16S; Sediments; Staphylococcus aureus; Staphylococcus infections; Taxonomy; Tuberculosis; natural products; drug discovery; antimicrobial resistance; Micromonospora; phocoenamicins; actinomycetes; polyketides; spirotetronates
• ISSN: 1660-3397; 1660-3397
• DOI: 10.3390/md20120769

Over the past few years, new technological and scientific advances have reinforced the field of natural product discovery. The spirotetronate class of natural products has recently grown with the discovery of phocoenamicins, natural actinomycete derived compounds that possess different antibiotic activities. Exploring the MEDINA's strain collection, 27 actinomycete strains, including three marine-derived and 24 terrestrial strains, were identified as possible phocoenamicins producers and their taxonomic identification by 16S rDNA sequencing showed that they all belong to the genus. Using an OSMAC approach, all the strains were cultivated in 10 different media each, resulting in 270 fermentations, whose extracts were analyzed by LC-HRMS and subjected to High-throughput screening (HTS) against methicillin-resistant (MRSA), H37Ra and . The combination of LC-UV-HRMS analyses, metabolomics analysis and molecular networking (GNPS) revealed that they produce several related spirotetronates not disclosed before. Variations in the culture media were identified as the most determining factor for phocoenamicin production and the best producer strains and media were established. Herein, we reported the chemically diverse production and metabolic profiling of sp. strains, including the known phocoenamicins and maklamicin, reported for the first time as being related to this family of compounds, as well as the bioactivity of their crude extracts. Although our findings do not confirm previous statements about phocoenamicins production only in unique marine environments, they have identified marine-derived species as the best producers of phocoenamicins in terms of both the abundance in their extracts of some major members of the structural class and the variety of molecular structures produced.