Heterologous Cellular Design for Complex Natural Product Support

Heterologous biosynthesis is a strategy for reconstituting production of complex natural products with potential applicability as anticancer agents, antibiotics, and in numerous other settings.  The host in these efforts provides some benefit relative to native production.  Innate advantages would allow rapid growth kinetics, a simple cellular morphology, and robust culture characteristics.  Additional features would include simple and expansive cellular manipulation protocols available to engineer and design the cell to support the numerous requirements for complex natural product biosynthesis.  In this presentation, E. coli will be discussed as model heterologous host for the production of complex natural products that span well-recognized polyketide, nonribosomal peptide, and isoprenoid classifications.  In particular, emphasis will be placed on ensuring successful reconstitution and how such lessons can enable the cell to be used in a discovery-oriented format for the purpose of both identifying, engineering, and overproducing valuable natural compounds.