Format

Send to

Choose Destination
Nat Chem Biol. 2014 Nov;10(11):963-8. doi: 10.1038/nchembio.1659. Epub 2014 Sep 28.

A roadmap for natural product discovery based on large-scale genomics and metabolomics.

Author information

1
Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA.
2
1] Department of Chemistry, Northwestern University, Evanston, Illinois, USA. [2] Department of Molecular Biosciences, Northwestern University, Evanston, Illinois, USA. [3] Feinberg School of Medicine, Northwestern University, Evanston, Illinois, USA.
3
Department of Microbiology, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA.
4
Bacterial Foodborne Pathogens and Mycology Research, US Department of Agriculture, Agricultural Research Service, National Center for Agricultural Utilization Research, Peoria, Illinois, USA.
5
1] Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA. [2] Department of Microbiology, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA.

Abstract

Actinobacteria encode a wealth of natural product biosynthetic gene clusters, whose systematic study is complicated by numerous repetitive motifs. By combining several metrics, we developed a method for the global classification of these gene clusters into families (GCFs) and analyzed the biosynthetic capacity of Actinobacteria in 830 genome sequences, including 344 obtained for this project. The GCF network, comprising 11,422 gene clusters grouped into 4,122 GCFs, was validated in hundreds of strains by correlating confident mass spectrometric detection of known small molecules with the presence or absence of their established biosynthetic gene clusters. The method also linked previously unassigned GCFs to known natural products, an approach that will enable de novo, bioassay-free discovery of new natural products using large data sets. Extrapolation from the 830-genome data set reveals that Actinobacteria encode hundreds of thousands of future drug leads, and the strong correlation between phylogeny and GCFs frames a roadmap to efficiently access them.

PMID:
25262415
PMCID:
PMC4201863
DOI:
10.1038/nchembio.1659
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center