Abstract: Most FDA-approved small molecule drugs are either natural products or inspired by natural products. In every case, microbes from all three domains of life, Archaea, Prokarya, and Eukarya, have been either identified as the producer of these secondary metabolites or speculated to be involved in their production via symbiotic associations. In the search for new microbial secondary metabolites, chemists have traditionally explored easily accessible terrestrial environments. However, by the 1990s, all of the “low hanging fruit” had been picked and natural product rediscovery rates increased. As a result, underexplored environments, such as extreme ecosystems, are now being investigated. The enzymes involved in the biosynthesis of these molecules can also be exploited and manipulated to produce new secondary metabolites. This seminar will discuss how the Giddings lab studies microbial natural product biosynthesis by bioprospecting acid mine drainage for new bioactive metabolites and elucidating the mechanisms of enzymes involved in siderophore biosynthesis. Understanding how Nature synthesizes natural products will provide insight into how to make new derivatives as well as improve their production for commercial, research, and clinical use.