Gene-Guided Discovery and Ribosomal Biosynthesis of Moroidin Peptides.

التفاصيل البيبلوغرافية
العنوان:	Gene-Guided Discovery and Ribosomal Biosynthesis of Moroidin Peptides.
المؤلفون:	Kersten RD; Department of Medicinal Chemistry, University of Michigan, Ann Arbor, Michigan 48109, United States., Mydy LS; Department of Medicinal Chemistry, University of Michigan, Ann Arbor, Michigan 48109, United States., Fallon TR; Whitehead Institute for Biomedical Research, 455 Main Street, Cambridge, Massachusetts 02142, United States.; Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, United States., de Waal F; Bioinformatics Group, Wageningen University, Wageningen 6700AP, The Netherlands., Shafiq K; Department of Medicinal Chemistry, University of Michigan, Ann Arbor, Michigan 48109, United States., Wotring JW; Department of Medicinal Chemistry, University of Michigan, Ann Arbor, Michigan 48109, United States., Sexton JZ; Department of Medicinal Chemistry, University of Michigan, Ann Arbor, Michigan 48109, United States.; Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan 48109, United States., Weng JK; Whitehead Institute for Biomedical Research, 455 Main Street, Cambridge, Massachusetts 02142, United States.; Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, United States.
المصدر:	Journal of the American Chemical Society [J Am Chem Soc] 2022 May 04; Vol. 144 (17), pp. 7686-7692. Date of Electronic Publication: 2022 Apr 19.
نوع المنشور:	Journal Article; Research Support, Non-U.S. Gov't
اللغة:	English
بيانات الدورية:	Publisher: American Chemical Society Country of Publication: United States NLM ID: 7503056 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1520-5126 (Electronic) Linking ISSN: 00027863 NLM ISO Abbreviation: J Am Chem Soc Subsets: MEDLINE
أسماء مطبوعة:	Publication: Washington, DC : American Chemical Society Original Publication: Easton, Pa. [etc.]
مواضيع طبية MeSH:	Peptides, Cyclic/chemistry , Tryptophan/metabolism, Australia ; Peptides/metabolism ; Peptides/pharmacology ; Plants ; Protein Processing, Post-Translational
مستخلص:	Moroidin is a bicyclic plant octapeptide with tryptophan side-chain cross-links, originally isolated as a pain-causing agent from the Australian stinging tree Dendrocnide moroides . Moroidin and its analog celogentin C, derived from Celosia argentea , are inhibitors of tubulin polymerization and, thus, lead structures for cancer therapy. However, low isolation yields from source plants and challenging organic synthesis hinder moroidin-based drug development. Here, we present biosynthesis as an alternative route to moroidin-type bicyclic peptides and report that they are ribosomally synthesized and posttranslationally modified peptides (RiPPs) derived from BURP-domain peptide cyclases in plants. By mining 793 plant transcriptomes for moroidin core peptide motifs within BURP-domain precursor peptides, we identified a moroidin cyclase in Japanese kerria, which catalyzes the installation of the tryptophan-indole-centered macrocyclic bonds of the moroidin bicyclic motif in the presence of cupric ions. Based on the kerria moroidin cyclase, we demonstrate the feasibility of producing diverse moroidins including celogentin C in transgenic tobacco plants and report specific cytotoxicity of celogentin C against a lung adenocarcinoma cancer cell line. Our study sets the stage for future biosynthetic development of moroidin-based therapeutics and highlights that mining plant transcriptomes can reveal bioactive cyclic peptides and their underlying cyclases from new source plants.
المشرفين على المادة:	0 (Peptides) 0 (Peptides, Cyclic) 0 (moroidin) 8DUH1N11BX (Tryptophan)
تواريخ الأحداث:	Date Created: 20220419 Date Completed: 20220505 Latest Revision: 20220601
رمز التحديث:	20221213
DOI:	10.1021/jacs.2c00014
PMID:	35438481
قاعدة البيانات:	MEDLINE

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تدمد:	1520-5126
DOI:	10.1021/jacs.2c00014