Performing Department
(N/A)
Non Technical Summary
Herbal medicine has been developed and practiced by multiple indigenous cultures around the world for millennia. In modern medicine, of the 175 therapeutic small molecules approved by FDA for treating cancer since 1940, 131, or 74.8%, are other than synthetic, with 85, or 48.6%, actually being either natural products or directly derived therefrom. Among natural products-derived modern medicines, 25% come from plants. Recent advances in fundamental knowledge of plant specialized metabolism and the ability to engineer plant natural product biosynthesis in heterologous hosts greatly expedite our ability to harness the medicinal values of plants to treat human diseases. In the project, we focus on two related classes of medicinal peptide natural products initially isolated from the Chinese medicinal plant Lycium barbarum (goji berry) and Dendrocnide moroides (Australian stinging tree). By elucidating and engineering the biosynthetic pathways for these natural products, this research will open up tremendous new opportunities for greatly expanding the chemical space of cyclic peptides through the means of synthetic biology approach for both agronomical and pharmaceutical applications.
Animal Health Component
(N/A)
Research Effort Categories
Basic
100%
Applied
(N/A)
Developmental
(N/A)
Goals / Objectives
The enormous chemodiversity present in plants has served as an endless source for therapeutic agents for treating human diseases. Lyciumins and moroidins are unique branched cyclic peptides found in plants with uncharacterized biosynthetic pathways. In this project, we aim to 1) elucidate the biosynthetic pathways of branched cyclic peptides in plants; 2) characterize the catalytic mechanisms and structure-function relationships of key branched cyclic peptide biosynthetic enzymes; and 3) engineer programmable cyclic peptide production systems in tobacco BY-2 cells. This research will open up tremendous new opportunities for greatly expanding the chemical space of cyclic peptides through the means of synthetic biology approach for both agronomical and pharmaceutical applications.
Project Methods
The project focuses on elucidating the biosynthesis of plant branched cyclic peptides, particularly lyciumins and moroidins, to leverage their therapeutic potential. The research employs a combination of genomics, biochemistry, and synthetic biology techniques. It involves transcriptome mining to identify precursor peptides, in vivo and in vitro experiments to characterize biosynthetic pathways, and engineering tobacco BY-2 cells for peptide production. The project uniquely departs from traditional methods by using plant systems for peptide diversification and bioengineering, offering scalable production of bioactive compounds. Results will be analyzed through metabolomic and proteomic profiling, structural biology, and enzymatic assays. The impact on the scientific community and potential applications in medicine and agriculture will be evaluated through the generation of novel cyclic peptides and insights into plant biochemistry, with outcomes disseminated through publications and a peptide library for broader research use.