title: An automated Genomes-to-Natural Products platform (GNP) for the discovery of modular natural products.
abstract: Bacterial natural products are a diverse and valuable group of small molecules, and genome sequencing indicates that the vast majority remain undiscovered. The prediction of natural product structures from biosynthetic assembly lines can facilitate their discovery, but highly automated, accurate, and integrated systems are required to mine the broad spectrum of sequenced bacterial genomes. Here we present a genome-guided natural products discovery tool to automatically predict, combinatorialize and identify polyketides and nonribosomal peptides from biosynthetic assembly lines using LC-MS/MS data of crude extracts in a high-throughput manner. We detail the directed identification and isolation of six genetically predicted polyketides and nonribosomal peptides using our Genome-to-Natural Products platform. This highly automated, user-friendly programme provides a means of realizing the potential of genetically encoded natural products.
authors.affiliation: Department of Biochemistry &Biomedical Sciences, M. G. DeGroote Institute for Infectious Disease Research; McMaster University, Hamilton, Ontario, Canada L8N 3Z5.|Department of Chemistry &Chemical Biology, M. G. DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, Ontario, Canada L8N 3Z5.
authors.forename: Chad W
authors.initials: CW
authors.lastname: Johnston
authors.affiliation: Department of Biochemistry &Biomedical Sciences, M. G. DeGroote Institute for Infectious Disease Research; McMaster University, Hamilton, Ontario, Canada L8N 3Z5.|Department of Chemistry &Chemical Biology, M. G. DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, Ontario, Canada L8N 3Z5.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Skinnider
authors.affiliation: Department of Biochemistry &Biomedical Sciences, M. G. DeGroote Institute for Infectious Disease Research; McMaster University, Hamilton, Ontario, Canada L8N 3Z5.|Department of Chemistry &Chemical Biology, M. G. DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, Ontario, Canada L8N 3Z5.
authors.forename: Morgan A
authors.initials: MA
authors.lastname: Wyatt
authors.affiliation: Department of Biochemistry &Biomedical Sciences, M. G. DeGroote Institute for Infectious Disease Research; McMaster University, Hamilton, Ontario, Canada L8N 3Z5.|Department of Chemistry &Chemical Biology, M. G. DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, Ontario, Canada L8N 3Z5.
authors.forename: Xiang
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Biochemistry &Biomedical Sciences, M. G. DeGroote Institute for Infectious Disease Research; McMaster University, Hamilton, Ontario, Canada L8N 3Z5.|Department of Chemistry &Chemical Biology, M. G. DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, Ontario, Canada L8N 3Z5.
authors.forename: Michael R M
authors.initials: MR
authors.lastname: Ranieri
authors.affiliation: The David R. Cheriton School of Computer Science, University of Waterloo, Waterloo, Ontario, Canada N2L 3G1.
authors.forename: Lian
authors.initials: L
authors.lastname: Yang
authors.affiliation: Department of Chemistry; Queens University, Kingston, Ontario, Canada K7L 3N6.
authors.forename: David L
authors.initials: DL
authors.lastname: Zechel
authors.affiliation: The David R. Cheriton School of Computer Science, University of Waterloo, Waterloo, Ontario, Canada N2L 3G1.
authors.forename: Bin
authors.initials: B
authors.lastname: Ma
authors.affiliation: Department of Biochemistry &Biomedical Sciences, M. G. DeGroote Institute for Infectious Disease Research; McMaster University, Hamilton, Ontario, Canada L8N 3Z5.|Department of Chemistry &Chemical Biology, M. G. DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, Ontario, Canada L8N 3Z5.
authors.forename: Nathan A
authors.initials: NA
authors.lastname: Magarvey
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry; D001688:Biological Products / Q000032:analysis*; D042621:Comamonadaceae / Q000737:chemistry; D055808:Drug Discovery / Q000379:methods*; D016680:Genome, Bacterial; D006031:Glycosylation; D057166:High-Throughput Screening Assays; D055666:Lipopeptides / Q000737:chemistry; D010455:Peptides / Q000032:analysis*; D061065:Polyketides / Q000032:analysis*; D012984:Software
chemical_list: D001426:Bacterial Proteins; D001688:Biological Products; D055666:Lipopeptides; D010455:Peptides; D061065:Polyketides; C000607810:thanamycin