Approaches to natural products discovery: case studies on Streptomyces spp.

Samenvatting

Compounds produced by living organisms - natural products - have been essential to human medicine. More than two thirds of antibiotics that we use today originate from microorganisms. Bacteria belonging to the Streptomyces genus have been an outstanding source of chemical compounds that not only fight infectious diseases but are also used to preserve food or protect crops. Yet, it is estimated that only 2% of metabolites that Streptomyces are capable of producing have been described.
In my thesis I investigated 20 diverse Streptomyces isolates, grew them in the lab, and compared the potential that was coded in their genomes to the potential that had materialized as metabolites. The aim of my work was to find chemically novel metabolites: in three chapters I describe three previously unknown compounds. Even though it is challenging to imagine the unseen, there are several strategies that can be effectively employed to discover novel chemical matter. Each of the three chapters deploys a distinct approach. My thesis manifests that chemical novelty can be successfully found by closely investigating a modest number of powerful organisms.