Exploring the Antibiotic Potential of Micromonospora

The term 'antibiotic' must be redefined because it is often used inaccurately and primarily reflects an outdated definition. Conventional understanding emphasizes antimicrobial properties. However, some data suggest that antibiotics are better characterized as 'pluripotent' agents due to their multifunctional qualities. This perspective enhances our understanding by illustrating that the emergence of antibiotic resistance is not confined to their activity against bacteria but should also consider other roles, such as antifungal, anticancer, and antiviral properties. Micromonospora, a genus in the Actinomycetota phylum, is well-known for its biosynthesis of medicinal bioactive compounds (Yan et al., ۲۰۲۲). Non-ribosomal peptides (NRPs), a significant source of secondary metabolites with various biological functions, play a crucial role in this process (Süssmuth & Mainz, ۲۰۱۷). Identifying novel compounds and enhancing our understanding of their biosynthesis pathways via genome mining techniques are essential for developing new therapeutic agents (Bauman et al., ۲۰۲۱). In this study, we analyzed the whole genomes of nine species of the Micromonospora genus using antiSMASH, a bioinformatics platform designed primarily for identifying and characterizing biosynthetic gene clusters (BGCs) (Blin et al., ۲۰۲۳). Microorganisms' annotations were sourced from BacDive (Bacterial Diversity Database), the largest repository providing standardized information on bacterial and archaeal strains (Schober et al., ۲۰۲۴). Of the ۱۸۵ identified regions containing a BGC, ۴۵ were linked to NRP production, with their applications further extracted from PubChem, ChEBI, and relevant articles. The wide range of applications includes antibacterial (۴۲%), siderophore (۱۲%), antitumor (۱۸%), antifungal (۶%), antiprotozoal (۶%), neuroprotective (۳%), antiviral (۳%), immunosuppressive (۳%), antioxidant (۳%), and anti-cardiovascular (۱%). Some compounds, such as Lymphostatin (an immunosuppressive compound), are distributed among all nine Micromonospora species. Concurrently, certain compounds were identified only within a single species, including Capreomycins, Clifednamide A, Clipibicyclene, Coprisamide, Disgocidine, Enduracidin, Enteromycin, Frankobactins, Griseobactin, Kosinostatin, Pacidamycins, Telomycin, Trichrysobactins, and Tyrobetaine. Significantly, over half of these bioactive compounds are classified as hybrid polyketide-NRP structures, exhibiting considerably greater bioactive potential than their NRP counterparts. For instance, hybrid compounds encompass neuroprotective, antifungal, antiviral, immunosuppressive, antioxidant, and anti-cardiovascular activities, along with nearly all antitumor properties. In contrast, hybrids account for half of the identified compounds related to antibiotics and siderophores. This study elucidates the biological roles and microbial annotations within the Micromonospora genus. It also emphasizes the genus's contribution to the production of bioactive chemicals with biotechnological applications, paving the way for discovering novel therapeutic medicines.

کلیدواژه ها:

genome mining ، Micromonospora ، antibiotics ، NRP ، antiSMASH ، BacDive