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Nucleic Acids Res. 2015 Nov 16;43(20):9645-62. doi: 10.1093/nar/gkv1012. Epub 2015 Oct 5.

Genomes to natural products PRediction Informatics for Secondary Metabolomes (PRISM).

Author information

1
Departments of Biochemistry and Biomedical Sciences and Chemistry and Chemical Biology, Michael G. DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, ON, L8S 4K1, Canada.
2
Departments of Biochemistry and Biomedical Sciences and Chemistry and Chemical Biology, Michael G. DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, ON, L8S 4K1, Canada magarv@mcmaster.ca.

Abstract

Microbial natural products are an invaluable source of evolved bioactive small molecules and pharmaceutical agents. Next-generation and metagenomic sequencing indicates untapped genomic potential, yet high rediscovery rates of known metabolites increasingly frustrate conventional natural product screening programs. New methods to connect biosynthetic gene clusters to novel chemical scaffolds are therefore critical to enable the targeted discovery of genetically encoded natural products. Here, we present PRISM, a computational resource for the identification of biosynthetic gene clusters, prediction of genetically encoded nonribosomal peptides and type I and II polyketides, and bio- and cheminformatic dereplication of known natural products. PRISM implements novel algorithms which render it uniquely capable of predicting type II polyketides, deoxygenated sugars, and starter units, making it a comprehensive genome-guided chemical structure prediction engine. A library of 57 tailoring reactions is leveraged for combinatorial scaffold library generation when multiple potential substrates are consistent with biosynthetic logic. We compare the accuracy of PRISM to existing genomic analysis platforms. PRISM is an open-source, user-friendly web application available at http://magarveylab.ca/prism/.

PMID:
26442528
PMCID:
PMC4787774
DOI:
10.1093/nar/gkv1012
[Indexed for MEDLINE]
Free PMC Article

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