Challenges and Opportunities in Discovery of Secondary Metabolites Using a Functional Metagenomic Approach

Abstract

Bioprospecting for natural products via a metagenomic approach has been highly successful for enzyme discovery, yet methodological challenges have inhibited discovery of diverse secondary metabolites from environmental metagenomes. In this chapter, we discuss metagenomic approaches to identify and/or express secondary metabolites encoded from environmental DNA. The application of next-generation sequencing techniques has generated enormous metagenomic sequence databases for polyketide synthases. Isolated biosynthetic pathways can be introduced into multiple heterologous hosts, with some hosts engineered for expression of specific pathways. The goal of tapping into the extant diversity of secondary metabolites encoded by environmental metagenomes is being enabled by a combination of approaches, including advances in NGS technology, cloning methods, high-throughput screening, development of improved heterologous hosts, and pathway engineering.