title: Using natural products for drug discovery: the impact of the genomics era.
abstract: Evolutionarily selected over billions of years for their interactions with biomolecules, natural products have been and continue to be a major source of pharmaceuticals. In the 1990s, pharmaceutical companies scaled down their natural product discovery programs in favor of synthetic chemical libraries due to major challenges such as high rediscovery rates, challenging isolation, and low production titers. Propelled by advances in DNA sequencing and synthetic biology technologies, insights into microbial secondary metabolism provided have inspired a number of strategies to address these challenges. Areas covered: This review highlights the importance of genomics and metagenomics in natural product discovery, and provides an overview of the technical and conceptual advances that offer unprecedented access to molecules encoded by biosynthetic gene clusters. Expert opinion: Genomics and metagenomics revealed nature's remarkable biosynthetic potential and her vast chemical inventory that we can now prioritize and systematically mine for novel chemical scaffolds with desirable bioactivities. Coupled with synthetic biology and genome engineering technologies, significant progress has been made in identifying and predicting the chemical output of biosynthetic gene clusters, as well as in optimizing cluster expression in native and heterologous host systems for the production of pharmaceutically relevant metabolites and their derivatives.
authors.affiliation: a Metabolic Engineering Research Laboratory , Science and Engineering Institutes, Agency for Science, Technology and Research (A*STAR) , Singapore , Singapore.
authors.forename: Mingzi M
authors.initials: MM
authors.lastname: Zhang
authors.affiliation: a Metabolic Engineering Research Laboratory , Science and Engineering Institutes, Agency for Science, Technology and Research (A*STAR) , Singapore , Singapore.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Qiao
authors.affiliation: a Metabolic Engineering Research Laboratory , Science and Engineering Institutes, Agency for Science, Technology and Research (A*STAR) , Singapore , Singapore.
authors.forename: Ee Lui
authors.initials: EL
authors.lastname: Ang
authors.affiliation: a Metabolic Engineering Research Laboratory , Science and Engineering Institutes, Agency for Science, Technology and Research (A*STAR) , Singapore , Singapore.|b Department of Chemical and Biomolecular Engineering , University of Illinois at Urbana-Champaign , Urbana , IL , USA.
authors.forename: Huimin
authors.initials: H
authors.lastname: Zhao
mesh_terms: D001688:Biological Products / Q000737:chemistry / Q000494:pharmacology*; D055808:Drug Discovery / Q000379:methods*; D004345:Drug Industry / Q000379:methods; D023281:Genomics / Q000379:methods*; D006801:Humans; D056186:Metagenomics / Q000379:methods; D005810:Multigene Family; D064210:Secondary Metabolism; D017422:Sequence Analysis, DNA; D054852:Small Molecule Libraries
chemical_list: D001688:Biological Products; D054852:Small Molecule Libraries
keywords: Genome mining; bioinformatics; biosynthetic gene clusters; metagenomics; secondary metabolites