Fungal natural products galaxy: Biochemistry and molecular genetics toward blockbuster drugs discovery.

Secondary metabolites synthesized by fungi have become a precious source of inspiration for the design of novel drugs. Indeed, fungi are prolific producers of fascinating, diverse, structurally complex, and low-molecular-mass natural products with high therapeutic leads, such as novel antimicrobial compounds, anticancer compounds, immunosuppressive agents, among others. Given that these microorganisms possess the extraordinary capacity to secrete diverse chemical scaffolds, they have been highly exploited by the giant pharma companies to generate small molecules. This has been made possible because the isolation of metabolites from fungal natural sources is feasible and surpasses the organic synthesis of compounds, which otherwise remains a significant bottleneck in the drug discovery process. Here in this comprehensive review, we have discussed recent studies on different fungi (pathogenic, non-pathogenic, commensal, and endophytic/symbiotic) from different habitats (terrestrial and marines), the specialized metabolites they biosynthesize, and the drugs derived from these specialized metabolites. Moreover, we have unveiled the logic behind the biosynthesis of vital chemical scaffolds, such as NRPS, PKS, PKS-NRPS hybrid, RiPPS, terpenoids, indole alkaloids, and their genetic mechanisms. Besides, we have provided a glimpse of the concept behind mycotoxins, virulence factor, and host immune response based on fungal infections.

Antibiotic drug discovery: Challenges and perspectives in the light of emerging antibiotic resistance.

Amid a rising threat of antimicrobial resistance in a global scenario, our huge investments and high-throughput technologies injected for rejuvenating the key therapeutic scaffolds to suppress these rising superbugs has been diminishing severely. This has grasped world-wide attention, with increased consideration being given to the discovery of new chemical entities. Research has now proven that the relatively tiny and simpler microbes possess enhanced capability of generating novel and diverse chemical constituents with huge therapeutic leads. The usage of these beneficial organisms could help in producing new chemical scaffolds that govern the power to suppress the spread of obnoxious superbugs. Here in this review, we have explicitly focused on several appealing strategies employed for the generation of new chemical scaffolds. Also, efforts on providing novel insights on some of the unresolved questions in the production of metabolites, metabolic profiling and also the serendipity of getting "hit molecules" have been rigorously discussed. However, we are highly aware that biosynthetic pathway of different classes of secondary metabolites and their biosynthetic route is a vast topic, thus we have avoided discussion on this topic.