S47: Challenges and strategies in streamlining the heterologous production of complex natural products

Using experience and insight gained from previous attempts at producing complex natural product compounds through heterologous hosts, this presentation will describe new initiatives to rapidly access the chemical products encoded by responsible genetic pathways.  The basis for the work presented is the polyketide antibiotic erythromycin A.  The heterologous production of erythromycin A through E. coli presented challenges in metabolic engineering to provide precursor biosynthetic support, gene expression to account for the coordinated production >20 enzymes dedicated to biosynthesis, and analytical chemistry to assess intermediate and final product levels.  Addressing each challenge is now positioning new technology to expedite production of this and other complex therapeutic natural products.  This talk will present ongoing efforts at rapidly reconstituting production of the erythromycin A compound through methods envisioned to be applied to future complex compounds in future heterologous production attempts.