title: Natural product proteomining, a quantitative proteomics platform, allows rapid discovery of biosynthetic gene clusters for different classes of natural products.
abstract: Information on gene clusters for natural product biosynthesis is accumulating rapidly because of the current boom of available genome sequencing data. However, linking a natural product to a specific gene cluster remains challenging. Here, we present a widely applicable strategy for the identification of gene clusters for specific natural products, which we name natural product proteomining. The method is based on using fluctuating growth conditions that ensure differential biosynthesis of the bioactivity of interest. Subsequent combination of metabolomics and quantitative proteomics establishes correlations between abundance of natural products and concomitant changes in the protein pool, which allows identification of the relevant biosynthetic gene cluster. We used this approach to elucidate gene clusters for different natural products in Bacillus and Streptomyces, including a novel juglomycin-type antibiotic. Natural product proteomining does not require prior knowledge of the gene cluster or secondary metabolite and therefore represents a general strategy for identification of all types of gene clusters.
authors.affiliation: Leiden Institute of Chemistry, Leiden University, 2300RA Leiden, the Netherlands.
authors.forename: Jacob
authors.initials: J
authors.lastname: Gubbens
authors.affiliation: Institute of Biology Leiden, Leiden University, 2300RA Leiden, the Netherlands.
authors.forename: Hua
authors.initials: H
authors.lastname: Zhu
authors.affiliation: Institute of Biology Leiden, Leiden University, 2300RA Leiden, the Netherlands.
authors.forename: Geneviève
authors.initials: G
authors.lastname: Girard
authors.affiliation: Department of Chemistry, University of Warwick, Coventry CV4 7AL, UK.
authors.forename: Lijiang
authors.initials: L
authors.lastname: Song
authors.affiliation: Leiden Institute of Chemistry, Leiden University, 2300RA Leiden, the Netherlands.
authors.forename: Bogdan I
authors.initials: BI
authors.lastname: Florea
authors.affiliation: Department of Chemistry, University of Warwick, Coventry CV4 7AL, UK.
authors.forename: Philip
authors.initials: P
authors.lastname: Aston
authors.affiliation: Research Institute of Pharmaceutical Sciences, Musashino University, Shinmachi, Nishitokyo-shi, Tokyo 202-8585, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Ichinose
authors.affiliation: Leiden Institute of Chemistry, Leiden University, 2300RA Leiden, the Netherlands.
authors.forename: Dmitri V
authors.initials: DV
authors.lastname: Filippov
authors.affiliation: Institute of Biology Leiden, Leiden University, 2300RA Leiden, the Netherlands.
authors.forename: Young H
authors.initials: YH
authors.lastname: Choi
authors.affiliation: Leiden Institute of Chemistry, Leiden University, 2300RA Leiden, the Netherlands.
authors.forename: Herman S
authors.initials: HS
authors.lastname: Overkleeft
authors.affiliation: Department of Chemistry, University of Warwick, Coventry CV4 7AL, UK.
authors.forename: Gregory L
authors.initials: GL
authors.lastname: Challis
authors.affiliation: Institute of Biology Leiden, Leiden University, 2300RA Leiden, the Netherlands. Electronic address: g.wezel@biology.leidenuniv.nl.
authors.forename: Gilles P
authors.initials: GP
authors.lastname: van Wezel
mesh_terms: D001688:Biological Products / Q000145:classification* / Q000378:metabolism*; D053898:Biosynthetic Pathways / Q000235:genetics*; D005810:Multigene Family; D011506:Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D040901:Proteomics
chemical_list: D001688:Biological Products; D011506:Proteins