Engineering of E. coli for heterologous expression of secondary metabolite biosynthesis pathways recovered from metagenomics libraries

A key component of the functional metagenomics approach for complex natural product discovery is the host system chosen to screen environmental DNA. The host must provide technical simplicity to enable high throughput assessment of the target compounds of interest. Furthermore, intracellular support is crucial to allowing biosynthesis of those compounds with the most chemical and bioactivity diversity. This chapter examines the characteristics of functional metagenomics screening hosts, including those historically used in discovery applications. An emphasis is placed on identifying desirable features of selected hosts and how engineering strategies may be applied to further enable the goals of compound discovery. A special emphasis is placed on the use of Streptomyces spp. and Escherichia coli as screening hosts and how the parallel field of heterologous biosynthesis engineering with these two hosts has interfaced with past and present objectives in functional metagenomics. Other screening hosts and future prospects for this component of metagenomics-based discovery are also discussed.