Microbial genome mining for accelerated natural products discovery: is a renaissance in the making?

Abstract

Microbial genome mining is a rapidly developing approach to discover new and novel secondary metabolites for drug discovery. Many advances have been made in the past decade to facilitate genome mining, and these are reviewed in this Special Issue of the Journal of Industrial Microbiology and Biotechnology. In this Introductory Review, we discuss the concept of genome mining and why it is important for the revitalization of natural product discovery; what microbes show the most promise for focused genome mining; how microbial genomes can be mined; how genome mining can be leveraged with other technologies; how progress on genome mining can be accelerated; and who should fund future progress in this promising field. We direct interested readers to more focused reviews on the individual topics in this Special Issue for more detailed summaries on the current state-of-the-art.

Fig. 1

Strategies for natural product discovery. a The historical ‘grind and find’ mechanism of secondary metabolite discovery. b Post-genomic discovery now seeks to leverage prescience of gene sequence data to improve the yield of discovery. c The extended central dogma as it relates to genome mining for secondary metabolism.

Fig. 2

Two major categories of approaches being investigated in genome mining efforts. In heterologous expression, whole gene clusters are mobilized into expression strains and differentially analyzed to identify new compounds. In homologous expression approaches, endogenous transcriptional, translational, or metabolic elements are manipulated, either by mutation or (bio)chemical stimulants to activate secondary metabolite production. In either case, the these approaches entail the labor intensive process of identification of new peaks within a metabolome and isolation of these compounds for structural elucidation.