Gene-guided discovery and engineering of branched cyclic peptides in plants
Name
E10961.full.pdf
Description
Published version
Size
903.62 KB
Format
Adobe PDF
Checksum (MD5)
36c6b0e8f09c18501fceb5a20739932b
Author(s)
Kersten, Roland D.
Weng, Jing-Ke
Date Issued
October 29, 2018
Journal
Proceedings of the National Academy of Sciences of the United States of America
Publisher
Proceedings of the National Academy of Sciences
Citation
Kersten, Roland D. and Jing-Ke Weng. "Gene-guided discovery and engineering of branched cyclic peptides in plants." Proceedings of the National Academy of Sciences of the United States of America 115 (2018): E10961-E10969 © 2019 The Author(s)
Version
Final published version
Abstract
The plant kingdom contains vastly untapped natural product chemistry, which has been traditionally explored through the activity-guided approach. Here, we describe a gene-guided approach to discover and engineer a class of plant ribosomal peptides, the branched cyclic lyciumins. Initially isolated from the Chinese wolfberry Lycium barbarum, lyciumins are protease-inhibiting peptides featuring an N-terminal pyroglutamate and a macrocyclic bond between a tryptophan-indole nitrogen and a glycine α-carbon. We report the identification of a lyciumin precursor gene from L. barbarum, which encodes a BURP domain and repetitive lyciumin precursor peptide motifs. Genome mining enabled by this initial finding revealed rich lyciumin genotypes and chemotypes widespread in flowering plants. We establish a biosynthetic framework of lyciumins and demonstrate the feasibility of producing diverse natural and unnatural lyciumins in transgenic tobacco. With rapidly expanding plant genome resources, our approach will complement bioactivity-guided approaches to unlock and engineer hidden plant peptide chemistry for pharmaceutical and agrochemical applications.
Subjects
Multidisciplinary
MIT Department
Massachusetts Institute of Technology. Department of Biology
Whitehead Institute for Biomedical Research
Terms of Use
Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
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DOI of Published Version
https://doi.org/10.1073/pnas.1813993115
