A Widely Distributed Biosynthetic Cassette Is Responsible for Diverse Plant Side Chain Cross‐Linked Cyclopeptides**

Abstract

Cyclopeptide alkaloids are an abundant class of plant cyclopeptides with over 200 analogs described and bioactivities ranging from analgesic to antiviral. While these natural products have been known for decades, their biosynthetic basis remains unclear. Using a transcriptome-mining approach, we link the cyclopeptide alkaloids from Ceanothus americanus to dedicated RiPP precursor peptides and identify new, widely distributed split BURP peptide cyclase containing gene clusters. Guided by our bioinformatic analysis, we identify and isolate new cyclopeptides from Coffea arabica, which we named arabipeptins. Reconstitution of the enzyme activity for the BURP found in the biosynthesis of arabipeptin A validates the activity of the newly discovered split BURP peptide cyclases. These results expand our understanding of the biosynthetic pathways responsible for diverse cyclic plant peptides and suggest that these side chain cross-link modifications are widely distributed in eudicots.

Jujube Fruit Metabolomic Profiles Reveal Cultivar Differences and Function as Cultivar Fingerprints

“…As mentioned above and also apparent from the pairwise metabolic comparison ( Table 1 ), a large diversity of specialized metabolites was detected in jujube fruits, including medicinal natural products. An example of a medicinal natural product class from Ziziphus plants is cyclopeptide alkaloids, a structurally diverse group of cyclic peptides biosynthesized through the ribosomal pathway by copper-dependent BURP peptide cyclases [ 16 ] and from predicted split precursor peptides co-localized on the Ziziphus genome to hypothetical peptide cyclase genes [ 17 , 47 ]. In the analyzed mature fruit metabolomes, we identified an analyte matching MS and tandem MS data literature values corresponding to sanjoinine A [ 48 ], a sedative cyclopeptide alkaloid from Ziziphus spinosa which has been characterized as a bioactive compound from jujube herbal medicine used to treat insomnia ( Figure 9 , Figure S6 ).…”

“…In addition, jujube is the source of many natural products with medicinal potential and application in herbal medicine. For example, cyclopeptide alkaloids, which are ribosomally synthesized and posttranslationally modified plant peptides [ 16 , 17 ], have been isolated in large chemical diversity from jujube species, including several compounds with medicinal activities such as anxiolytic sanjoinine A and antiviral jubanine H [ 18 , 19 , 20 , 21 , 22 ]. A cationic peptide called Snakin-Z has also been reported to possess antimicrobial properties in the species [ 23 ].…”

Deciphering metabolomics mechanism explaining the role of secondary metabolites as an aid in improving the agronomic traits and tolerance against several stress

“…At genomic region 8, ribosomal synthesized and post-translationally modi ed peptides (RiPPs) are abundant from 2,720,609-2,730,899. These diverse peptide classes are responsible for several biological translation processes and their post-modi cation in response to stress [33,34].…”