Genomic Enzymology

Web Tools for Leveraging Protein Family Sequence-Function Space and Genome Context to Discover Novel Functions

Research output: Contribution to journalArticle

Abstract

The exponentially increasing number of protein and nucleic acid sequences provides opportunities to discover novel enzymes, metabolic pathways, and metabolites/natural products, thereby adding to our knowledge of biochemistry and biology. The challenge has evolved from generating sequence information to mining the databases to integrating and leveraging the available information, i.e., the availability of "genomic enzymology" web tools. Web tools that allow identification of biosynthetic gene clusters are widely used by the natural products/synthetic biology community, thereby facilitating the discovery of novel natural products and the enzymes responsible for their biosynthesis. However, many novel enzymes with interesting mechanisms participate in uncharacterized small-molecule metabolic pathways; their discovery and functional characterization also can be accomplished by leveraging information in protein and nucleic acid databases. This Perspective focuses on two genomic enzymology web tools that assist the discovery novel metabolic pathways: (1) Enzyme Function Initiative-Enzyme Similarity Tool (EFI-EST) for generating sequence similarity networks to visualize and analyze sequence-function space in protein families and (2) Enzyme Function Initiative-Genome Neighborhood Tool (EFI-GNT) for generating genome neighborhood networks to visualize and analyze the genome context in microbial and fungal genomes. Both tools have been adapted to other applications to facilitate target selection for enzyme discovery and functional characterization. As the natural products community has demonstrated, the enzymology community needs to embrace the essential role of web tools that allow the protein and genome sequence databases to be leveraged for novel insights into enzymological problems.

Original languageEnglish (US)
Pages (from-to)4293-4308
Number of pages16
JournalBiochemistry
Volume56
Issue number33
DOIs
StatePublished - Aug 22 2017

Fingerprint

Genes
Genome
Biological Products
Enzymes
Metabolic Networks and Pathways
Proteins
Fungal Genome
Nucleic acid sequences
Microbial Genome
Synthetic Biology
Protein Databases
Biochemistry
Biosynthesis
Nucleic Acid Databases
Multigene Family
Metabolites
Nucleic Acids
Sequence Analysis
Availability
Databases

ASJC Scopus subject areas

  • Biochemistry

Cite this

@article{4438b788fa294075b6329859e936f9f5,
title = "Genomic Enzymology: Web Tools for Leveraging Protein Family Sequence-Function Space and Genome Context to Discover Novel Functions",
abstract = "The exponentially increasing number of protein and nucleic acid sequences provides opportunities to discover novel enzymes, metabolic pathways, and metabolites/natural products, thereby adding to our knowledge of biochemistry and biology. The challenge has evolved from generating sequence information to mining the databases to integrating and leveraging the available information, i.e., the availability of {"}genomic enzymology{"} web tools. Web tools that allow identification of biosynthetic gene clusters are widely used by the natural products/synthetic biology community, thereby facilitating the discovery of novel natural products and the enzymes responsible for their biosynthesis. However, many novel enzymes with interesting mechanisms participate in uncharacterized small-molecule metabolic pathways; their discovery and functional characterization also can be accomplished by leveraging information in protein and nucleic acid databases. This Perspective focuses on two genomic enzymology web tools that assist the discovery novel metabolic pathways: (1) Enzyme Function Initiative-Enzyme Similarity Tool (EFI-EST) for generating sequence similarity networks to visualize and analyze sequence-function space in protein families and (2) Enzyme Function Initiative-Genome Neighborhood Tool (EFI-GNT) for generating genome neighborhood networks to visualize and analyze the genome context in microbial and fungal genomes. Both tools have been adapted to other applications to facilitate target selection for enzyme discovery and functional characterization. As the natural products community has demonstrated, the enzymology community needs to embrace the essential role of web tools that allow the protein and genome sequence databases to be leveraged for novel insights into enzymological problems.",
author = "Gerlt, {John Alan}",
year = "2017",
month = "8",
day = "22",
doi = "10.1021/acs.biochem.7b00614",
language = "English (US)",
volume = "56",
pages = "4293--4308",
journal = "Biochemistry",
issn = "0006-2960",
publisher = "American Chemical Society",
number = "33",

}

TY - JOUR

T1 - Genomic Enzymology

T2 - Web Tools for Leveraging Protein Family Sequence-Function Space and Genome Context to Discover Novel Functions

AU - Gerlt, John Alan

PY - 2017/8/22

Y1 - 2017/8/22

N2 - The exponentially increasing number of protein and nucleic acid sequences provides opportunities to discover novel enzymes, metabolic pathways, and metabolites/natural products, thereby adding to our knowledge of biochemistry and biology. The challenge has evolved from generating sequence information to mining the databases to integrating and leveraging the available information, i.e., the availability of "genomic enzymology" web tools. Web tools that allow identification of biosynthetic gene clusters are widely used by the natural products/synthetic biology community, thereby facilitating the discovery of novel natural products and the enzymes responsible for their biosynthesis. However, many novel enzymes with interesting mechanisms participate in uncharacterized small-molecule metabolic pathways; their discovery and functional characterization also can be accomplished by leveraging information in protein and nucleic acid databases. This Perspective focuses on two genomic enzymology web tools that assist the discovery novel metabolic pathways: (1) Enzyme Function Initiative-Enzyme Similarity Tool (EFI-EST) for generating sequence similarity networks to visualize and analyze sequence-function space in protein families and (2) Enzyme Function Initiative-Genome Neighborhood Tool (EFI-GNT) for generating genome neighborhood networks to visualize and analyze the genome context in microbial and fungal genomes. Both tools have been adapted to other applications to facilitate target selection for enzyme discovery and functional characterization. As the natural products community has demonstrated, the enzymology community needs to embrace the essential role of web tools that allow the protein and genome sequence databases to be leveraged for novel insights into enzymological problems.

AB - The exponentially increasing number of protein and nucleic acid sequences provides opportunities to discover novel enzymes, metabolic pathways, and metabolites/natural products, thereby adding to our knowledge of biochemistry and biology. The challenge has evolved from generating sequence information to mining the databases to integrating and leveraging the available information, i.e., the availability of "genomic enzymology" web tools. Web tools that allow identification of biosynthetic gene clusters are widely used by the natural products/synthetic biology community, thereby facilitating the discovery of novel natural products and the enzymes responsible for their biosynthesis. However, many novel enzymes with interesting mechanisms participate in uncharacterized small-molecule metabolic pathways; their discovery and functional characterization also can be accomplished by leveraging information in protein and nucleic acid databases. This Perspective focuses on two genomic enzymology web tools that assist the discovery novel metabolic pathways: (1) Enzyme Function Initiative-Enzyme Similarity Tool (EFI-EST) for generating sequence similarity networks to visualize and analyze sequence-function space in protein families and (2) Enzyme Function Initiative-Genome Neighborhood Tool (EFI-GNT) for generating genome neighborhood networks to visualize and analyze the genome context in microbial and fungal genomes. Both tools have been adapted to other applications to facilitate target selection for enzyme discovery and functional characterization. As the natural products community has demonstrated, the enzymology community needs to embrace the essential role of web tools that allow the protein and genome sequence databases to be leveraged for novel insights into enzymological problems.

UR - http://www.scopus.com/inward/record.url?scp=85028013309&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85028013309&partnerID=8YFLogxK

U2 - 10.1021/acs.biochem.7b00614

DO - 10.1021/acs.biochem.7b00614

M3 - Article

VL - 56

SP - 4293

EP - 4308

JO - Biochemistry

JF - Biochemistry

SN - 0006-2960

IS - 33

ER -