Natural products produced by Streptomyces bacteria have played a central role in the discovery of antibiotics, anticancer agents, and other therapeutically important compounds. Despite their historical success, the discovery of new natural products has slowed. This is partly because many of the gene clusters that encode natural product biosynthesis remain silent under laboratory conditions, and partly because structural diversification of existing scaffolds remains challenging. At the same time, advances in genome mining, metabolomics, and biosynthetic engineering have revealed vast unexplored biosynthetic potential, creating new opportunities for accessing previously hidden chemical diversity. This doctoral thesis aimed to harness biosynthetic diversity in Streptomyces through complementary strategies that activate metabolite production and expand natural product chemical diversity. First, microbial interactions were used as ecological triggers to induce secondary metabolism. Physical interactions between Streptomyces and yeast stimulated the production of antifungal polyene metabolites and revealed strain-specific metabolic responses associated with microbial competition, demonstrating how ecological interactions can activate otherwise silent biosynthetic pathways. Second, biosynthetic engineering strategies were applied to diversify natural product scaffolds. Engineering of deoxysugar biosynthesis pathways enabled the generation of a diverse panel of glycosylated tetracenomycin derivatives, including four previously unreported analogues, providing insight into how glycosylation influences structural diversity and biological activity. Third, enzyme-level engineering of anthracycline methyltransferases generated 20 engineered enzymes and led to the production of a new anthracycline derivative, illustrating how modification of tailoring enzymes can expand structural diversity within clinically important natural product families. Together, this thesis demonstrates how ecological activation and biosynthetic engineering can reveal and expand the chemical diversity of Streptomyces natural products. These findings support systematic approaches for accessing biosynthetic potential and reinforce microbial natural products as a source of novel drug leads.