Natural products genomics

Abstract

Secondary metabolites (or natural products) are often synthesized by multi‐modular, multi‐domain proteins called non‐ribosomal peptide synthetases (NRPS) and polyketide synthases (PKS). Various well‐known metabolites produced by microorganisms are listed in Table 1, and examples of structures are shown in Fig. 1. In particular, Streptomyces species are known for their ability to produce a wide variety of secondary metabolites such as antibiotics, herbicides, parasitocides, siderophores and pharmacologically active substances including antitumour agents and immunosuppressants. Genome sequencing of Streptomyces coelicolor (Bentley et al., 2002) and S. avermitilis (Omura et al., 2001) revealed over 20 gene clusters for biosynthesis of secondary metabolites, while only a few of their natural products were known prior to sequencing. High‐throughput genome sequencing of hundreds of other bacterial species and strains is now rapidly increasing the repertoire of identified gene clusters for biosynthesis of natural products (Donadio et al., 2007). Here we give a brief update of the current status of genome mining and bioinformatic tools to identify novel NRPS and PKS systems. Table 1 Examples of microbial natural products produced by NRPS/PKS systems. Figure 1 Examples of some chemical structures of (A) polyketides, (B) non‐ribosomal peptides and (C) mixed NRP‐PK compounds. Reprinted with permission from Watanabe and Oikawa (2007). Copyright Royal Society of Chemistry.