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Preferred
(EDT)

4189161 - Biosynthesis of 14-membered Ziziphus cyclopeptide alkaloids | Poster Board #877

3:00 PM - 5:00 PM EDT
Tuesday, March 25, 2025Room: Hall B2/C (San Diego Convention Center)
Parent Session
Current Topics in Biochemistry and Chemical Biology:
Room: Hall B2/C (San Diego Convention Center)
DIVISION/COMMITTEE: [BIOL: Division of Biochemistry and Chemical Biology]
Credits
0.00 CE
Organizers
Poster - In-person
BIOL: Division of Biochemistry and Chemical Biology
Overview
Cyclopeptide alkaloids are ribosomally synthesized and post-translationally modified peptide (RiPP) natural products that are attractive compounds for pharmaceutical discovery as they are highly diversified, poses drug-like properties, and exhibit broad biomedical activities such as neuroactive sanjoinine A from Ziziphus jujuba. Cyclopeptide alkaloids are defined by N-terminal alkylation, a C-terminal styrylamine motif, and 13-, 14-, or 15-membered rings with either a para- or meta-phenol ether-crosslink. Organic synthesis of cyclopeptide alkaloids is challenged by the formation of small macrocycles and the styrylamine moiety whereas isolation from source plants provides low yields.
Recent advances in omics-guided elucidation of plant natural product biosynthetic pathways have enabled biosynthetic access to complex plant metabolites and their precursors for semisynthesis. The Kersten group identified plant-specific BURP-domain proteins that catalyze the peptide macrocyclization of aromatic amino acid side chains with unactivated carbons in a copper-dependent reaction to form cyclopeptide alkaloids. Building on this discovery, we describe here the discovery of biosynthetic enzymes towards the biosynthetic production and diversification of 14-membered cyclopeptide alkaloids such as sanjoinine A by mining genomes and transcriptomes of Ziziphus jujuba.