همایش ملی بیوانفورماتیک ایران

صفحه اصلی / 4th international edition and 13th Iranian Conference on Bioinformatics

Exploring the Antibiotic Potential of Micromonospora

نویسندگان :

Niloufar Zamanpour¹ Najmeh Salehi² Javad Hamedi³

1- دانشگاه تهران 2- دانشگاه تهران 3- دانشگاه تهران

کلمات کلیدی :

Genome mining،Micromonospora،antibiotics،NRP،antiSMASH

چکیده :

The term "antibiotic" is often misunderstood and is largely based on an outdated explanation, necessitating a renewed definition. Conventional knowledge primarily focuses on its antimicrobial function. However, various findings highlight that antibiotics are better described as "pluripotent" agents due to their multifunctional properties. This perspective should deepen our understanding, showing that the emergence of antibiotic resistance is not limited to their activity against bacteria but should also consider other functions, such as antifungal, anticancer, and antiviral properties. Micromonospora, a genus within the Actinomycetota phylum, is widely recognized for biosynthesizing medicinal bioactive products (Yan et al., 2022). Notably, non-ribosomal peptides (NRPs) play a significant role in this process. This enriched source of secondary metabolites exhibits a variety of biological activities. Genome mining methods are instrumental in uncovering novel compounds and enhancing our understanding of their biosynthetic pathways, leading to identifying novel therapeutic agents.(Bauman et al., 2021) 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., 2023). Microorganisms’ annotations were sourced from BacDive (Bacterial Diversity Database), which is the largest repository providing standardized information on bacterial and archaeal strains (Schober et al., 2024). Of the 185 identified regions containing a BGC, 45 were linked to NRP production, with their applications further extracted from PubChem, ChEBI, and relevant articles. The wide range of applications includes antibacterial (50%), siderophore (18%), antitumor (27%), antifungal (1%), neuroprotective (1%), antiviral (1%), immunosuppressive (1%), and anti-cardiovascular (1%). Fifty percent of the bioactive compounds are identified as hybrid compounds combined with polyketide, while the remainder are NRP. Hybrids exhibit greater bioactive potential. For instance, all neuroprotectant, antifungal, and antiviral compounds, as well as 62.5% of antitumor compounds, are hybrid polyketide-NRP. However, the percentage of hybrid compounds drops to 42% and 50% for antibiotic and siderophore respectively. Some compounds, e.g., lymphostatin (an immunosuppressive compound) are distributed in all nine Micromonospora species while, some others were found in only one species, such as clifednamide A, clipibicyclene, coprisamide, disgocidine, frankobactins, griseobactin, kosinostatin, pacidamycins, telomycin, trichrysobactins, and tyrobetaine. The most significant finding of this research is that hybrids possess the highest potential for producing compounds with pluripotent functional activities. This research sheds light on the diverse biological functions and microbial annotations of the Micromonospora genus, particularly emphasizing its role in producing bioactive compounds with biotechnological applications, opening the way for finding new therapeutic agents.