Abstract: The preparation of macrocyclic molecules from linear, synthetic thioester precursors is disclosed. An excised thioesterase domain isolated from either a polyketide synthases (PKS) or non-ribosomal peptide synthetases (NRPS) multido system catalyzes the cyclization reaction. Thioester substrates also are described that are efficiently cyclized by the method of the present invention. Additionally, macrocyclic molecules, including macrolactones and macrolactams, that are prepared by the macrocyclization methods of the invention are described.

Abstract: The invention features a new solid supports having at least one amino functionality and a linker bound to the solid support through at least a portion of the amino functional groups. The invention also features solid support bound substrates suitable for use in the formation of macrocycles by a TE domain catalyzed macrocyclization reaction. The invention features methods of making the solid supports and solid support bound substrates of the invention and methods of effecting macrocyclizations of solid support bound substrates. The invention further provides new macrocyclic molecules having one or more peptide domains and one or more polyketide domains in the macrocyclic ring. In another embodiment of the invention, libraries of macrocycles are provided as well as methods of forming libraries of macrocycles from libraries of solid support bound substrates are provided.

Abstract: The preparation of macrocyclic molecules from linear, synthetic thioester precursors is disclosed. An excised thioesterase domain isolated from either a PKS or NRPS multidomain system catalyzes the cyclization reaction. Thioester substrates also are described that are efficiently cyclized by the method of the present invention. Additionally, macrocyclic molecules, including macrolactones and macrolactams, that are prepared by the macrocyclization methods of the invention are described.