Natural product proteomining, a quantitative proteomics platform, allows rapid discovery of biosynthetic gene clusters for different classes of natural products

Jacob Gubbens, Hua Zhu, Geneviève Girard, Lijiang Song, Bogdan I. Florea, Philip Aston, Koji Ichinose, Dmitri V. Filippov, Young H. Choi, Herman S. Overkleeft, Gregory L. Challis, Gilles P. Van Wezel

Research output: Contribution to journalArticleResearchpeer-review

34 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)707-718
Number of pages12
JournalChemistry and Biology
Volume21
Issue number6
DOIs
Publication statusPublished - 19 Jun 2014
Externally publishedYes

Cite this

Gubbens, J., Zhu, H., Girard, G., Song, L., Florea, B. I., Aston, P., Ichinose, K., Filippov, D. V., Choi, Y. H., Overkleeft, H. S., Challis, G. L., & Van Wezel, G. P. (2014). Natural product proteomining, a quantitative proteomics platform, allows rapid discovery of biosynthetic gene clusters for different classes of natural products. Chemistry and Biology, 21(6), 707-718. https://doi.org/10.1016/j.chembiol.2014.03.011