Use of Inteins for the In Vivo Production of Stable Cyclic Peptide Libraries in E. coli

Advances and opportunities in drug discovery and functional genomics have put methods for generating molecular diversity at a premium. Both chemical and biological approaches for the production of compound libraries have been pursued. Combinatorial chemistry has been used to synthesize molecular libraries in vitro, while molecular biology has been exploited to biosynthesize molecular libraries within cells. Unlike synthetic methods, which have largely focused on the production of libraries of small molecules, biosynthetic libraries must contend with the catabolic machinery of the host cell. Thus, variable segments are typically embedded within or fused to large biomolecules (1 ). The resulting random sequences have been described as peptides, but they display the physical characteristic of the scaffold biopolymer.