@article{906b066a5cdc42ff8b48e370019698d5,
title = "Correlative metabologenomics of 110 fungi reveals metabolite–gene cluster pairs",
abstract = "Natural products research increasingly applies -omics technologies to guide molecular discovery. While the combined analysis of genomic and metabolomic datasets has proved valuable for identifying natural products and their biosynthetic gene clusters (BGCs) in bacteria, this integrated approach lacks application to fungi. Because fungi are hyper-diverse and underexplored for new chemistry and bioactivities, we created a linked genomics–metabolomics dataset for 110 Ascomycetes, and optimized both gene cluster family (GCF) networking parameters and correlation-based scoring for pairing fungal natural products with their BGCs. Using a network of 3,007 GCFs (organized from 7,020 BGCs), we examined 25 known natural products originating from 16 known BGCs and observed statistically significant associations between 21 of these compounds and their validated BGCs. Furthermore, the scalable platform identified the BGC for the pestalamides, demystifying its biogenesis, and revealed more than 200 high-scoring natural product–GCF linkages to direct future discovery. [Figure not available: see fulltext.]",
author = "Caesar, {Lindsay K.} and Butun, {Fatma A.} and Robey, {Matthew T.} and Ayon, {Navid J.} and Raveena Gupta and David Dainko and Bok, {Jin Woo} and Grant Nickles and Stankey, {Robert J.} and Don Johnson and David Mead and Cank, {Kristof B.} and Earp, {Cody E.} and Raja, {Huzefa A.} and Oberlies, {Nicholas H.} and Keller, {Nancy P.} and Kelleher, {Neil L.}",
note = "Funding Information: Genome sequencing for this project was conducted at the Roy J. Carver Biotechnology Center at the University of Illinois-Urbana-Champaign. This research was supported in part by the National Institutes of Health grant nos. F32 GM132679 to L.K.C., R01 GM112739-05A1 to N.P.K., T32 GM135066 to G.N., R44 AI140943-03 to J.W.B., P01 CA125066 to N.H.O. and 2R01 AT009143 to N.L.K. This work also made use of the IMSERC NMR facility at Northwestern University, which has received support from the Soft and Hybrid Nanotechnology Experimental Resource (grant no. NSF ECCS-2025633) grant. Figures 1, 4 and 5 were created using BioRender.com . Funding Information: Genome sequencing for this project was conducted at the Roy J. Carver Biotechnology Center at the University of Illinois-Urbana-Champaign. This research was supported in part by the National Institutes of Health grant nos. F32 GM132679 to L.K.C., R01 GM112739-05A1 to N.P.K., T32 GM135066 to G.N., R44 AI140943-03 to J.W.B., P01 CA125066 to N.H.O. and 2R01 AT009143 to N.L.K. This work also made use of the IMSERC NMR facility at Northwestern University, which has received support from the Soft and Hybrid Nanotechnology Experimental Resource (grant no. NSF ECCS-2025633) grant. Figures 1, 4 and 5 were created using BioRender.com. Publisher Copyright: {\textcopyright} 2023, The Author(s), under exclusive licence to Springer Nature America, Inc.",
year = "2023",
month = jul,
doi = "10.1038/s41589-023-01276-8",
language = "English (US)",
volume = "19",
pages = "846--854",
journal = "Nature Chemical Biology",
issn = "1552-4450",
publisher = "Nature Publishing Group",
number = "7",
}