{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Vinogradov AA"],"funding":["Japan Agency for Medical Research and Development","Japan Society for the Promotion of Science"],"pagination":["20332-20341"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9650704"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["144(44)"],"pubmed_abstract":["Bioengineering of ribosomally synthesized and post-translationally modified peptides (RiPPs) is an emerging approach to explore the diversity of pseudo-natural product structures for drug discovery purposes. However, despite the initial advances in this area, bioactivity reprogramming of multienzyme RiPP biosynthetic pathways remains a major challenge. Here, we report a platform for de novo discovery of functional thiopeptides based on reengineered biosynthesis of lactazole A, a RiPP natural product assembled by five biosynthetic enzymes. The platform combines in vitro biosynthesis of lactazole-like thiopeptides and mRNA display to prepare and screen large (≥10<sup>12</sup>) combinatorial libraries of pseudo-natural products. We demonstrate the utility of the developed protocols in an affi"],"journal":["Journal of the American Chemical Society"],"pubmed_title":["De Novo Discovery of Thiopeptide Pseudo-natural Products Acting as Potent and Selective TNIK Kinase Inhibitors."],"pmcid":["PMC9650704"],"funding_grant_id":["JP21H04712","JP16H06444","JP19K22243","JP20H05618","JP20K15407","JP19am0101070","JP20H02866"],"pubmed_authors":["Hamada K","Nishimura H","Terasaka N","Zhang Y","Goto Y","Sengoku T","Suga H","Vinogradov AA","Onaka H","Okada C","Ogata K","Chang JS"],"additional_accession":[]},"is_claimable":false,"name":"De Novo Discovery of Thiopeptide Pseudo-natural Products Acting as Potent and Selective TNIK Kinase Inhibitors.","description":"Bioengineering of ribosomally synthesized and post-translationally modified peptides (RiPPs) is an emerging approach to explore the diversity of pseudo-natural product structures for drug discovery purposes. However, despite the initial advances in this area, bioactivity reprogramming of multienzyme RiPP biosynthetic pathways remains a major challenge. Here, we report a platform for de novo discovery of functional thiopeptides based on reengineered biosynthesis of lactazole A, a RiPP natural product assembled by five biosynthetic enzymes. The platform combines in vitro biosynthesis of lactazole-like thiopeptides and mRNA display to prepare and screen large (≥10<sup>12</sup>) combinatorial libraries of pseudo-natural products. We demonstrate the utility of the developed protocols in an affi","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Nov","modification":"2026-05-31T23:07:47.76Z","creation":"2025-04-04T21:00:48.047Z"},"accession":"S-EPMC9650704","cross_references":{"pubmed":["36282922"],"doi":["10.1021/jacs.2c07937"]}}