Nature has gifted bacteria of the genus Streptomyces with immense metabolic potential, especially in their ability to produce a diverse array of natural products and enzymes. Many classes of natural products with antibiotic, antifungal, and anticancer
activities were discovered in the 20th century and continue to be widely used in modern medicine. However, our demand for novel drugs continues to grow, while the rate of new molecule discovery steadily declines. Furthermore, Streptomyces remains a valuable source of industrially relevant enzymes with applications from the food industry to sustainable biofuel production.

My doctoral research aimed to harness the full biosynthetic potential encoded in Streptomyces genomes by applying diverse, but complementary strategies to activate natural products biosynthetic pathways and improve enzyme production. Microbial
interactions with yeasts served as a potent natural trigger to induce the biosynthesis of multiple antifungal polyene compounds and yeast cell wall-degrading, carbohydrate-active enzymes. Through the combined use of microscopy, transcriptomics, and enzymatic activity assays, the study showed that Streptomyces deploys natural products and extracellular enzymes to degrade the cell walls and membranes of co-existing microorganisms, suggesting a form of facultative predatory behavior.

In addition, we developed single-cell mutant selection (SCMS) for targeted activation of silent biosynthetic gene clusters. SCMS, which integrates traditional random mutagenesis with reporter-guided selection and ultra-high-throughput
screening, was particularly efficient in enhancing product yields. This was demonstrated by a 22.8-fold increase in cholesterol oxidase production without the need to optimize growth conditions, resulting in higher yields than through classical heterologous expression in Streptomyces or Escherichia coli model hosts. The method was also shown to be useful in increasing yields of natural products by an order of magnitude, demonstrating broad utility for pharmaceutical and biotechnological applications, particularly in the development of industrially applicable microbes