For the past 25 years, I have devoted most of my research efforts to the ap
plication of molecular genetics to yield improvement and production of nove
l secondary metabolites in actinomycetes. My group at Lilly Research Labora
tories worked with a variety of Streptomyces species and with strains of Am
ycolatopsis and Saccharopolyspora. We developed molecular genetic tools to
manipulate actinomycete genes, and applied them to important secondary meta
bolites, including tylosin, daptomycin, vancomycin, chloroeremomycin, and s
pinosyns. In the early years, I helped establish recombinant DNA technology
to manufacture mammalian proteins, and more recently, helped implement mic
robial genomics as a research tool for antibiotic discovery. In this paper,
I review some highlights, primarily from the actinomycete work.