TY - JOUR
T1 - Using natural products for drug discovery
T2 - the impact of the genomics era
AU - Zhang, Mingzi M.
AU - Qiao, Yuan
AU - Ang, Ee Lui
AU - Zhao, Huimin
N1 - Publisher Copyright:
© 2017 Informa UK Limited, trading as Taylor & Francis Group.
PY - 2017/5/4
Y1 - 2017/5/4
N2 - Introduction: 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.
AB - Introduction: 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.
KW - Genome mining
KW - bioinformatics
KW - biosynthetic gene clusters
KW - metagenomics
KW - secondary metabolites
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U2 - 10.1080/17460441.2017.1303478
DO - 10.1080/17460441.2017.1303478
M3 - Review article
C2 - 28277838
AN - SCOPUS:85017549714
SN - 1746-0441
VL - 12
SP - 475
EP - 487
JO - Expert Opinion on Drug Discovery
JF - Expert Opinion on Drug Discovery
IS - 5
ER -