## 1 Introduction  
Bioactive microbial natural products are considered a prolific source of new drugs to combat infectious diseases and cancers. Starting with the discovery of penicillin from _Penicillium notatum_ in 1928, over 23,000 microbial compounds with antibacterial, immunosuppressive, antifungal, and cytotoxic activities have been reported, of which 42% account for fungi and 32% for bacteria [1]. Around 78% of antibacterial compounds and 74% of anticancer agents are related to natural products [2]. Due to overexploitation, the number of compounds extracted from terrestrial-borne microbes has significantly reduced over the last three decades [3]. Notably, the emergence of antimicrobial resistance among pathogens and tumoral resistance to chemotherapy is a growing public health challenge [4]. Therefore,there is an urgent need to discover novel bioactive compounds to better meet clinical therapeutic needs. _Streptomyces_ spp. are filamentous, sporulating, Gram-positive, and the largest genus of phylum Actinobacteria, and have gained significant attention due to their functions and essential role in clinical treatments and agriculture [2]. As of 2025, 908 species with validly published names have been reported at the time of writing ([[https://lpsn.dsmz.de/genus/streptomycinyces](https://lpsn.dsmz.de/genus/streptomycinyces)]([https://lpsn.dsmz.de/genus/streptomycinyces](https://lpsn.dsmz.de/genus/streptomycinyces)), accessed on 21 May 2025) [5]. Four novel _Streptomyces_ spp., including _Streptomyces caledonius_, _Streptomyces machaire_, _Streptomyces pratisoli_, and _Streptomyces achmelvichensis_, isolated from machair grassland soil, were recently proposed [6]. It is worth noting that the genus _Streptomyces_ secretes the majority of secondary metabolites with antibacterial, anticancer, antioxidant, and antiviral activities [7]. Approximately 70% of antibiotics available in the market are synthesized by _Streptomyces_ spp. [8], with some of them serving as anticancer, antioxidant, antiviral, and immunosuppressive agents [9]. Previously, doxorubicin, antimycin, and bagremycin act as anticancer compounds to treat different types of cancer cells, while streptomycin, chloramphenicol, and chloretracycline are common antibiotics to treat infectious diseases [2; 3]. Recently, guangnanmycin was shown to be a newly characterized member of the leinamycin family of sulfur-containing natural products, first identified in _Streptomyces_ sp. CB01883, a strain isolated from soil in Guangnan County, China [10]. It also contains a quinone moiety, which is capable of undergoing redox cycling and generating reactive oxygen species (ROS). Several studies have shown that quinone-containing compounds can induce apoptosis in human cancer cells through ROS generation, making guangnanmycin a promising candidate for anticancer drug development [11; 12; 13]. Despite the high rediscovery rate of known molecules due to the traditional method used and low production in nature, the isolation and characterization of novel and efficient _Streptomyces_ strains for medicinal and pharmaceutical sectors are still an area of active interest in the current scenario. Recent advances in next-generation sequencing have allowed rapid and cost-effective _Streptomyces_ genome sequencing, paving a new way for natural product research [14]. Different from other bacterial genera, the _Streptomyces_ chromosome is linear with a size that ranges from 6 to 12 Mb, encoding 5300 to 11,000 coding sequences (CDSs) [15]. The large genome is attributed to horizontal gene transfer, gene duplications, and recombination [15; 16]. Importantly, most compounds are synthesized by biosynthetic gene clusters (BGCs), which contain catalytic enzymes essential for the biosynthesis of secondary metabolites. Genome mining, as a new approach to identify previously unknown BGCs, demonstrated that at least 17 BGCs are present in _Streptomyces_ chromosomes; most of the BGCs are totally silent or cryptic when cultivated under normal laboratory culture conditions [17].