(12a) Heterologous Expression of Three Tetracycline Biosynthetic Pathways and Identification of New Tailoring Enzymes

Tetracyclines are members of the polyketide family produced by microbial sources. The chemical complexity of tetracyclines leads to a variety of biological activities including antibacterial, anticancer and activities against tetracycline resistant strains. Therefore, understanding the biosynthesis of tetracyclines not only provides genetic and biochemical insights but also sets the stage to engineer biosynthesis for generating new tetracycline analogs. To this end, we here report the heterologous expression of three structurally diverse tetracyclines and the identification of a number of new tailoring enzymes that can modify the tetracycline scaffold.