{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Wang X"],"funding":["Pharmaceutical Research and Manufacturers of America Foundation (PhRMA Foundation)","U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS)","U.S. Department of Health & Human Services | NIH | NIH Office of the Director (OD)"],"pagination":["4198"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12056006"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["16(1)"],"pubmed_abstract":["Nearly 10,000 plant species are represented by RNA-seq datasets in the NCBI sequence read archive, which are difficult to search in unassembled format due to database size. Here, we optimize RNA-seq assembly to transform most of this public RNA-seq data to a searchable database for biosynthetic gene discovery. We test our transcriptome mining pipeline towards the diversification of moroidins, which are plant ribosomally-synthesized and posttranslationally-modified peptides (RiPPs) biosynthesized from copper-dependent peptide cyclases. Moroidins are bicyclic compounds with a conserved stephanotic acid scaffold, which becomes cytotoxic to non-small cell lung adenocarcinoma cells with an additional C-terminal macrocycle. We discover moroidin analogs with second ring structures diversified at "],"journal":["Nature communications"],"pubmed_title":["Large-scale transcriptome mining enables macrocyclic diversification and improved bioactivity of the stephanotic acid scaffold."],"pmcid":["PMC12056006"],"funding_grant_id":["T32GM140223","S10OD034245","R35GM146934","R01GM152417","F32GM146395","Predoctoral Fellowship","F31GM155959"],"pubmed_authors":["Sexton JZ","Shafiq K","Mydy LS","Chigumba DN","Davis D","Kersten RD","Wang X","McDonough KM","Ousley DA"],"additional_accession":[]},"is_claimable":false,"name":"Large-scale transcriptome mining enables macrocyclic diversification and improved bioactivity of the stephanotic acid scaffold.","description":"Nearly 10,000 plant species are represented by RNA-seq datasets in the NCBI sequence read archive, which are difficult to search in unassembled format due to database size. Here, we optimize RNA-seq assembly to transform most of this public RNA-seq data to a searchable database for biosynthetic gene discovery. We test our transcriptome mining pipeline towards the diversification of moroidins, which are plant ribosomally-synthesized and posttranslationally-modified peptides (RiPPs) biosynthesized from copper-dependent peptide cyclases. Moroidins are bicyclic compounds with a conserved stephanotic acid scaffold, which becomes cytotoxic to non-small cell lung adenocarcinoma cells with an additional C-terminal macrocycle. We discover moroidin analogs with second ring structures diversified at ","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 May","modification":"2026-06-02T21:00:24.378Z","creation":"2026-04-20T03:14:34.821Z"},"accession":"S-EPMC12056006","cross_references":{"pubmed":["40328797"],"doi":["10.1038/s41467-025-59428-4"]}}