Progress 12/15/23 to 12/14/24
Outputs
Target Audience:The target audiences for this project include academic researchers, industry professionals, and broader scientific and agricultural communities interested in plant-derived therapeutics, synthetic biology, and metabolic engineering. Researchers in the fields of natural product chemistry, plant biology, and bioengineering benefit from the project's elucidation of previously uncharacterized biosynthetic pathways for branched cyclic peptides, advancing fundamental understanding of plant specialized metabolism. Pharmaceutical scientists and biotechnology professionals gain insights into novel enzyme mechanisms and biosynthetic strategies that can inform drug discovery and biomanufacturing of medicinal peptides. Agricultural researchers and crop scientists interested in engineering plant-based production platforms are also key beneficiaries, as the project explores the use of tobacco BY-2 cells for scalable peptide biosynthesis. Additionally, the research contributes to training graduate students and postdoctoral fellows through direct mentorship, laboratory instruction, and participation in interdisciplinary collaborations, helping to build expertise in biosynthetic pathway discovery and synthetic biology. By engaging with industry stakeholders and potential commercialization partners, the project also fosters technology transfer opportunities that could lead to novel biopharmaceutical or agronomic applications. Overall, this work has broad implications for advancing plant-based biomanufacturing and expanding the chemical space of medicinal peptides for both therapeutic and agricultural use. Changes/Problems:
Nothing Reported
What opportunities for training and professional development has the project provided?The project has provided training opportunities for one graduate student, one technician, and one postdoc in the areas of natural product chemistry, enzymology, plant cell biotechnology, and synthetic biology. How have the results been disseminated to communities of interest?The results of this research have been disseminated through multiple channels to ensure broad accessibility and impact within the scientific community and beyond. Findings have been shared through peer-reviewed publications, including: Reinhardt JK, Craft D, Weng JK. (2025) Toward an integrated omics approach for plant biosynthetic pathway discovery in the age of AI. Trends Biochem Sci. DOI:10.1016/j.tibs.2025.01.010. Suh EM, Reinhardt JK, Weng JK. (2024) The emergence and loss of cyclic peptides in Nicotiana illuminate dynamics and mechanisms of plant metabolic evolution. bioRxiv 2024.11.29.626059. (accepted atProc Natl Acad Sci U S A) Additionally, the PI has presented research supported by this grant in various conference and seminar What do you plan to do during the next reporting period to accomplish the goals?In the next reporting period, we will continue to work on the crystallization of various lyciumin biosynthetic enzymes and study the structure-function relationships of these enzymes in substrate recognition and catalysis. We will focus on identifying specific cyclic peptides that convey crop protection and medicinal properties through our bioassays.
Impacts
What was accomplished under these goals?
During this reporting period, we reported the discovery of nanamins, a novel class of burpitide-type cyclic peptides, and the resurrection of a pseudogenized precursor gene (ΨNatBURP2) in Nicotiana attenuata, restoring its enzymatic function. Structural and mutagenesis studies demonstrated the evolutionary divergence of nanamin and lyciumin biosynthesis, revealing key catalytic mechanisms. Heterologous expression in Nicotiana benthamiana validated the production of cyclic peptides, paving the way for synthetic biology applications. Ongoing work aims to elucidate the full biosynthetic cascade, engineer tobacco BY-2 cells for scalable peptide production, and explore bioactivities for pharmaceutical and agricultural applications. This research advances the understanding of plant-derived cyclic peptides and their potential for bioengineering novel therapeutics.
Publications
- Type:
Peer Reviewed Journal Articles
Status:
Accepted
Year Published:
2024
Citation:
Suh EM, Reinhardt JK, Weng JK. (2024) The emergence and loss of cyclic peptides in Nicotiana illuminate dynamics and mechanisms of plant metabolic evolution. bioRxiv 2024.11.29.626059. (accepted at Proc Natl Acad Sci U S A)
- Type:
Peer Reviewed Journal Articles
Status:
Published
Year Published:
2025
Citation:
Reinhardt JK, Craft D, Weng JK. (2025) Toward an integrated omics approach for plant biosynthetic pathway discovery in the age of AI. Trends Biochem Sci. DOI:10.1016/j.tibs.2025.01.010.
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