Unravelling the Chemical Diversity of Actinobacteria Obtained from Unique Asian Ecological Niches

Abstract

Actinobacteria play a vital role in pharmaceutical drug discovery therefore they are even considered as nature’s pharmacists. This phylum of bacteria has been very prolific in the production of secondary metabolites and many thereof are used in the form of medicines serving the humankind. Most of the drugs that get prescribed today are mimics of nature that researchers around the globe were capable to understand. However, there is still a lot to discover and learn from the nature. In our study, we have relied on the concept that bioprospecting strains from underexplored geographical locations and unique Asian niches which will in return offer the opportunity of finding novel compounds for pharmaceutical purposes. Following this approach, we designed a work to isolate strains from various ecological niches of Nepal, which is still a virgin land in terms of natural product research. This attempt represents therefore the pioneering work where we used Nepalese isolates to identify novel chemistry. Nepal has a varied climate and a broad bandwidth of altitudes (100 – 8849 meter) within in a short distance. These unique features make it one of the most biodiverse countries in all of Asia. Therefore, the first part of the thesis will mainly focus on soil-borne Streptomyces isolated from Nepal and their chemical analysis using a metabolomics-based workflow. Similarly, this study is continued with the investigation of the chemistry of rare actinomycetes isolated this time from a mud dauber wasp nests which are used as a traditional medicine in some parts of Nepal. The second part of the thesis describes the isolation and structure elucidation of nucleoside antibiotics from the marine strain, Streptomyces sp. SHP-22-7 isolated from the underexplored Enggano Island, Indonesia. In this study four novel structures belonging to plicacetin/amicetin family were identified with a combined genomics and metabolomics approach. Upon bioactivity analysis, the isolated pure compounds possessed an anti-mycobacterial activity. Furthermore, we have also probed successfully the concept of precursor directed biosynthesis to generate novel unnatural plicacetin derivatives.