Abstract: The present invention provides a method for merging combinatorial biosynthesis with techniques of synthetic organic chemistry. In general, this method, combinatorial biology, involves 1) providing “starter units”, wherein the starter units are capable of being accepted by the modular biosynthetic enzymatic machinery, and have incorporated therein a “functional handle” capable of reacting with specific functionality present on a solid support; 2) feeding these “starter units” into the modular biosynthetic enzymatic machinery, in vivo or in vitro, to obtain complex template molecules; and 3) further functionalizing the complex template molecules using synthetic organic chemistry to provide a collection of complex “unnatural” natural products having structural, topological, stereochemical and functional diversity. In one preferred embodiment, the starter units are attached to solid support units prior to being exposed to the modular biosynthetic enzymatic machinery.

Abstract: The present invention provides novel alkaloid compounds and collections of these compounds, and provides methods for the synthesis of these compounds using biomimetic synthetic strategies. Additionally, the present invention provides pharmaceutical compositions and methods for treating disorders such as bacterial infections, proliferative diseases, and reproductive disorders, to name a few.

Abstract: An in vivo assay system for identifying chemical compounds that inhibit or promote a biological event is described. Test compounds may be assayed for their ability to induce the expression of a reporter gene which subsequently leads to the production of a reporter gene product. Preferably the reporter gene product is secreted from the cell or is membrane permeable so that the product is readily detectable. The signal from the reporter gene is preferably amplifiable so that even minute changes in expression of the reporter gene are detectable. The present invention also provided combinatorial libraries for use in the inventive assay system.