Gene-guided discovery and engineering of branched cyclic peptides in plants
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 f...
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| Veröffentlicht in: | Proceedings of the National Academy of Sciences - PNAS 2018-11, Vol.115 (46), p.E10961-E10969 |
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| container_end_page | E10969 |
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| container_issue | 46 |
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| container_title | Proceedings of the National Academy of Sciences - PNAS |
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| creator | Kersten, Roland D. Weng, Jing-Ke |
| description | 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. |
| doi_str_mv | 10.1073/pnas.1813993115 |
| format | Article |
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| subjects | Biological activity Biological Sciences Engineers Feasibility studies Flowering Genes Genomes Genotype & phenotype Genotypes Glycine Lycium barbarum Natural products Nitrogen Organic chemistry Peptides Physical Sciences Plants (botany) PNAS Plus Precursors Tobacco Transgenic plants Tryptophan |
| title | Gene-guided discovery and engineering of branched cyclic peptides in plants |
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