Using genomics for natural product structure elucidation

Jonathan I. Tietz, Douglas Alan Mitchell

Research output: Contribution to journalReview article

Abstract

Natural products (NPs) are the most historically bountiful source of chemical matter for drug development—especially for anti-infectives. With insights gleaned from genome mining, interest in natural product discovery has been reinvigorated. An essential stage in NP discovery is structural elucidation, which sheds light not only on the chemical composition of a molecule but also its novelty, properties, and derivatization potential. The history of structure elucidation is replete with techniquebased revolutions: combustion analysis, crystallography, UV, IR, MS, and NMR have each provided game-changing advances; the latest such advance is genomics. All natural products have a genetic basis, and the ability to obtain and interpret genomic information for structure elucidation is increasingly available at low cost to non-specialists. In this review, we describe the value of genomics as a structural elucidation technique, especially from the perspective of the natural product chemist approaching an unknown metabolite. Herein we first introduce the databases and programs of interest to the natural products chemist, with an emphasis on those currently most suited for general usability. We describe strategies for linking observed natural product-linked phenotypes to their corresponding gene clusters. We then discuss techniques for extracting structural information from genes, illustrated with numerous case examples. We also provide an analysis of the biases and limitations of the field with recommendations for future development. Our overview is not only aimed at biologically-oriented researchers already at ease with bioinformatic techniques, but also, in particular, at natural product, organic, and/or medicinal chemists not previously familiar with genomic techniques.

Original languageEnglish (US)
Pages (from-to)1645-1694
Number of pages50
JournalCurrent Topics in Medicinal Chemistry
Volume16
Issue number15
StatePublished - Jun 1 2016

Fingerprint

Genomics
Biological Products
Crystallography
Multigene Family
Computational Biology
History
Research Personnel
Genome
Databases
Phenotype
Costs and Cost Analysis
Pharmaceutical Preparations
Genes

Keywords

  • Bioinformatics
  • Genome mining
  • Genomics
  • Metabolism
  • Natural products
  • Structural elucidation
  • Structure prediction

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Using genomics for natural product structure elucidation. / Tietz, Jonathan I.; Mitchell, Douglas Alan.

In: Current Topics in Medicinal Chemistry, Vol. 16, No. 15, 01.06.2016, p. 1645-1694.

Research output: Contribution to journalReview article

@article{6a848868d1f1442a83aa96ce492efb83,
title = "Using genomics for natural product structure elucidation",
abstract = "Natural products (NPs) are the most historically bountiful source of chemical matter for drug development—especially for anti-infectives. With insights gleaned from genome mining, interest in natural product discovery has been reinvigorated. An essential stage in NP discovery is structural elucidation, which sheds light not only on the chemical composition of a molecule but also its novelty, properties, and derivatization potential. The history of structure elucidation is replete with techniquebased revolutions: combustion analysis, crystallography, UV, IR, MS, and NMR have each provided game-changing advances; the latest such advance is genomics. All natural products have a genetic basis, and the ability to obtain and interpret genomic information for structure elucidation is increasingly available at low cost to non-specialists. In this review, we describe the value of genomics as a structural elucidation technique, especially from the perspective of the natural product chemist approaching an unknown metabolite. Herein we first introduce the databases and programs of interest to the natural products chemist, with an emphasis on those currently most suited for general usability. We describe strategies for linking observed natural product-linked phenotypes to their corresponding gene clusters. We then discuss techniques for extracting structural information from genes, illustrated with numerous case examples. We also provide an analysis of the biases and limitations of the field with recommendations for future development. Our overview is not only aimed at biologically-oriented researchers already at ease with bioinformatic techniques, but also, in particular, at natural product, organic, and/or medicinal chemists not previously familiar with genomic techniques.",
keywords = "Bioinformatics, Genome mining, Genomics, Metabolism, Natural products, Structural elucidation, Structure prediction",
author = "Tietz, {Jonathan I.} and Mitchell, {Douglas Alan}",
year = "2016",
month = "6",
day = "1",
language = "English (US)",
volume = "16",
pages = "1645--1694",
journal = "Current Topics in Medicinal Chemistry",
issn = "1568-0266",
publisher = "Bentham Science Publishers B.V.",
number = "15",

}

TY - JOUR

T1 - Using genomics for natural product structure elucidation

AU - Tietz, Jonathan I.

AU - Mitchell, Douglas Alan

PY - 2016/6/1

Y1 - 2016/6/1

N2 - Natural products (NPs) are the most historically bountiful source of chemical matter for drug development—especially for anti-infectives. With insights gleaned from genome mining, interest in natural product discovery has been reinvigorated. An essential stage in NP discovery is structural elucidation, which sheds light not only on the chemical composition of a molecule but also its novelty, properties, and derivatization potential. The history of structure elucidation is replete with techniquebased revolutions: combustion analysis, crystallography, UV, IR, MS, and NMR have each provided game-changing advances; the latest such advance is genomics. All natural products have a genetic basis, and the ability to obtain and interpret genomic information for structure elucidation is increasingly available at low cost to non-specialists. In this review, we describe the value of genomics as a structural elucidation technique, especially from the perspective of the natural product chemist approaching an unknown metabolite. Herein we first introduce the databases and programs of interest to the natural products chemist, with an emphasis on those currently most suited for general usability. We describe strategies for linking observed natural product-linked phenotypes to their corresponding gene clusters. We then discuss techniques for extracting structural information from genes, illustrated with numerous case examples. We also provide an analysis of the biases and limitations of the field with recommendations for future development. Our overview is not only aimed at biologically-oriented researchers already at ease with bioinformatic techniques, but also, in particular, at natural product, organic, and/or medicinal chemists not previously familiar with genomic techniques.

AB - Natural products (NPs) are the most historically bountiful source of chemical matter for drug development—especially for anti-infectives. With insights gleaned from genome mining, interest in natural product discovery has been reinvigorated. An essential stage in NP discovery is structural elucidation, which sheds light not only on the chemical composition of a molecule but also its novelty, properties, and derivatization potential. The history of structure elucidation is replete with techniquebased revolutions: combustion analysis, crystallography, UV, IR, MS, and NMR have each provided game-changing advances; the latest such advance is genomics. All natural products have a genetic basis, and the ability to obtain and interpret genomic information for structure elucidation is increasingly available at low cost to non-specialists. In this review, we describe the value of genomics as a structural elucidation technique, especially from the perspective of the natural product chemist approaching an unknown metabolite. Herein we first introduce the databases and programs of interest to the natural products chemist, with an emphasis on those currently most suited for general usability. We describe strategies for linking observed natural product-linked phenotypes to their corresponding gene clusters. We then discuss techniques for extracting structural information from genes, illustrated with numerous case examples. We also provide an analysis of the biases and limitations of the field with recommendations for future development. Our overview is not only aimed at biologically-oriented researchers already at ease with bioinformatic techniques, but also, in particular, at natural product, organic, and/or medicinal chemists not previously familiar with genomic techniques.

KW - Bioinformatics

KW - Genome mining

KW - Genomics

KW - Metabolism

KW - Natural products

KW - Structural elucidation

KW - Structure prediction

UR - http://www.scopus.com/inward/record.url?scp=84964284465&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84964284465&partnerID=8YFLogxK

M3 - Review article

C2 - 26456468

AN - SCOPUS:84964284465

VL - 16

SP - 1645

EP - 1694

JO - Current Topics in Medicinal Chemistry

JF - Current Topics in Medicinal Chemistry

SN - 1568-0266

IS - 15

ER -