The evolution of genome mining in microbes – a review

Abstract

Covering: 2006 to 2016The computational mining of genomes has become an important part in the discovery of novel natural products as drug leads. Thousands of bacterial genome sequences are publically available these days containing an even larger number and diversity of secondary metabolite gene clusters that await linkage to their encoded natural products. With the development of high-throughput sequencing methods and the wealth of DNA data available, a variety of genome mining methods and tools have been developed to guide discovery and characterisation of these compounds. This article reviews the development of these computational approaches during the last decade and shows how the revolution of next generation sequencing methods has led to an evolution of various genome mining approaches, techniques and tools. After a short introduction and brief overview of important milestones, this article will focus on the different approaches of mining genomes for secondary metabolites, from detecting biosynthetic genes to resistance based methods and "evo-mining" strategies including a short evaluation of the impact of the development of genome mining methods and tools on the field of natural products and microbial ecology.

The natural productome

“…Moreover, the reported results for cyanobacteria support the notion that looking at new producing organisms causes a burst in discovery of structurally novel natural products (9,10). Evidence suggests that investigating the same producing organism using new discovery tools, such as genome mining, should yield similarly productive bursts (11), as each genome encodes on average 25 secondary metabolites, only a few of which are known (8). This finding may help explain the interesting data from Pye et al (4) that shows a decreasing trend in structural similarity of newly discovered natural products from Streptomyces in the past few decades.…”

The Tripod for Bacterial Natural Product Discovery: Genome Mining, Silent Pathway Induction, and Mass Spectrometry-Based Molecular Networking

“…Particularly, compounds of microbial origin play a central role in this context, especially in the therapeutic areas of cancer and infectious diseases and as immunomodulatory drugs (1, 2). Among microbes, bacterial secondary metabolites are in the spotlight due to their simple genome organization and to the advances in genome sequencing and mining (3), as well as for their—in theory—facile biosynthetic pathway manipulation and laboratory cultivation (4). …”

“…Even in well-known secondary metabolite producers, the organization of BGCs coding for secondary metabolites is being reviewed, and unexpected biosynthetic setups are being found (11). This new information is constantly incorporated into the bioinformatics platforms for mining bacterial genomes and extracting the candidate secondary metabolites that these organisms can produce and vice versa (3). Therefore, we expect that genome mining will increasingly contribute to secondary metabolite discovery.…”

Toward Systems Metabolic Engineering of Streptomycetes for Secondary Metabolites Production

“…[32][33][34] In addition, to aid scientists within the field in prioritizing the individual tools, The Secondary Metabolite Bioinformatics Portal (SMBP) at http://www.secondary metabolites.org was recently launched. [35] For each tool or database, SMBP provides the users with links and short descriptions, allowing for quick and easy browsing.…”