Using natural products for drug discovery: the impact of the genomics era

Mingzi M. Zhang, Yuan Qiao, Ee Lui Ang, Huimin Zhao

Research output: Contribution to journalReview article

Abstract

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.

Original languageEnglish (US)
Pages (from-to)475-487
Number of pages13
JournalExpert Opinion on Drug Discovery
Volume12
Issue number5
DOIs
StatePublished - May 4 2017

Fingerprint

Drug Discovery
Genomics
Biological Products
Synthetic Biology
Metagenomics
Multigene Family
Small Molecule Libraries
Secondary Metabolism
Technology
Expert Testimony
DNA Sequence Analysis
Pharmaceutical Preparations
Genome
Equipment and Supplies

Keywords

  • Genome mining
  • bioinformatics
  • biosynthetic gene clusters
  • metagenomics
  • secondary metabolites

ASJC Scopus subject areas

  • Drug Discovery

Cite this

Using natural products for drug discovery : the impact of the genomics era. / Zhang, Mingzi M.; Qiao, Yuan; Ang, Ee Lui; Zhao, Huimin.

In: Expert Opinion on Drug Discovery, Vol. 12, No. 5, 04.05.2017, p. 475-487.

Research output: Contribution to journalReview article

Zhang, Mingzi M. ; Qiao, Yuan ; Ang, Ee Lui ; Zhao, Huimin. / Using natural products for drug discovery : the impact of the genomics era. In: Expert Opinion on Drug Discovery. 2017 ; Vol. 12, No. 5. pp. 475-487.
@article{f24723542da146b291dc4cf61e576d36,
title = "Using natural products for drug discovery: the impact of the genomics era",
abstract = "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.",
keywords = "Genome mining, bioinformatics, biosynthetic gene clusters, metagenomics, secondary metabolites",
author = "Zhang, {Mingzi M.} and Yuan Qiao and Ang, {Ee Lui} and Huimin Zhao",
year = "2017",
month = "5",
day = "4",
doi = "10.1080/17460441.2017.1303478",
language = "English (US)",
volume = "12",
pages = "475--487",
journal = "Expert Opinion on Drug Discovery",
issn = "1746-0441",
publisher = "Informa Healthcare",
number = "5",

}

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

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

UR - http://www.scopus.com/inward/record.url?scp=85017549714&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85017549714&partnerID=8YFLogxK

U2 - 10.1080/17460441.2017.1303478

DO - 10.1080/17460441.2017.1303478

M3 - Review article

C2 - 28277838

AN - SCOPUS:85017549714

VL - 12

SP - 475

EP - 487

JO - Expert Opinion on Drug Discovery

JF - Expert Opinion on Drug Discovery

SN - 1746-0441

IS - 5

ER -