Postdoctoral Fellowship: PRFB: Investigating the biosynthesis and evolution of mesembrine alkaloids in Sceletium

This action funds an NSF Plant Genome Postdoctoral Research Fellowship in Biology for FY 2024. The fellowship supports a research and training plan in a host laboratory for the Fellow who also presents a plan to broaden participation in biology. The title of the research and training plan for this fellowship to Dr.

Colin Y. Kim is “Investigating the Biosynthesis and Evolution of Mesembrine Alkaloids in Sceletium”. The host institution for the fellowship is Harvard University, and the sponsoring scientist is Dr. Ryan S. Nett.

Plants synthesize various biochemicals to help them develop, adapt and survive various stresses experienced in their growth environment. Often, these molecules are unique to a group of species. The rich molecular diversity present in plants provides a wide variety of valuable chemicals for food, nutrition, biofuels, and pharmaceuticals.

Despite more than 400,000 plant species generating over 200,000 natural products, there is still limited understanding of the intricate biosynthetic pathways responsible for their production and the context for their emergence in a group of plant species. In particular, the complex structures of nitrogen-containing alkaloids produced by plants have not been extensively explored.

This project aims to address this challenge by investigating how Sceletium plants build complex alkaloid chemical structures. This information is needed to discover plant biocatalysts and genomic signatures that can be harnessed to improve the production of valuable alkaloids for biomanufacturing and bioeconomy. The Fellow will receive training in genomics, chemical biosynthesis, and bioinformatics from this project.

To facilitate scientific communication and promote community participation, the fellow will engage students from the Boston Area schools on science outreach and provide opportunities for undergraduates from the host institution on experiential learning on scientific research. The Fellow will also mentor students performing scientific research and disseminate plant metabolism research through organizing the 2025 Gordon Research Seminar for Plant Metabolic Engineering and a natural product biosynthesis mini-symposium in the Boston-area focus group.

The fellowship will focus on the biosynthesis of mesembrine alkaloids, using it as a model to investigate key catalytic steps in alkaloid scaffold formation and their metabolic evolution in Sceletium tortuosum. The specific objectives include 1) probing the metabolic landscape and transcriptome of Sceletium to elucidate the biosynthetic pathway of mesembrine alkaloids and 2) examining the Sceletium genome to identify genomic signatures for convergent evolution of mesembrine alkaloid biosynthesis.

The Fellow will leverage metabolomics, transcriptomics, genomics, structural biology, and bioinformatics approaches to gain a comprehensive understanding of mesembrine biosynthesis. The omics datasets generated from this project will be accessible to the public through various community resource-sharing websites including the raw nucleotide sequencing reads on NCBI Sequence Read Archive and gene annotation data on NCBI BioStudies repositories.

This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.