ChemBio seminar by Dr. Anna Love - Scripps Institution of Oceanography; UC San Diego - CH 637
Event details
| Date | 04.07.2025 |
| Hour | 16:15 › 17:15 |
| Speaker | Dr. Anna Love |
| Location | |
| Category | Conferences - Seminars |
| Event Language | English |
Title:
Biosynthesis and biological mechanisms of minor cannabinoids
Abstract :
The study of natural products has enabled major insights into the biology of the brain, from discovery of new classes of receptors, to therapeutic starting points for neurological disease. For example, the endocannabinoid system, a signalling network comprising two receptors and a handful of bioactive lipids, was discovered through investigations into the molecular basis for Cannabis psychoactivity from Δ9-tetrahydrocannabinol (Δ9-THC). However, much remains to be learned about plant cannabinoids (phytocannabinoids) beyond Δ9-THC and cannabidiol (CBD), two of >110 cannabinoids produced in plants, and the physiological intersections of endo- and phytocannabinoid biology, including whether such interactions can be taken advantage of for selective pharmacological manipulation. First, I will address access to plant cannabinoids beyond Δ9-THC and CBD, which are generated natively in low quantities, and thus referred to as “minor cannabinoids.” I discovered that two marine bacterial flavoenzymes, Clz9 and Tcz9, possessed the unique ability to perform electrocyclization chemistry to generate the minor cannabinoid, cannabichromene (CBC) and analogues with high yield in bacteria. This provides a complementary route to isolation or synthetic chemistry to access material. Structural and mechanistic analysis revealed unique biochemistry governing the cannabinoid-cyclization chemistry of Clz9 and Tcz9, and established their utility as new members of the berberine-bridge like enzyme family. Complementary substrate-level engineering and active site restructuring improved the stereoselectivity of CBC-formation, providing enantiopure material. Further enzyme engineering efforts guided by a substrate-bound structure and a high-throughput screening platform seek to repurpose Clz9 and Tcz9 for production of cannabinoids beyond CBC, including THC-type and CBD-type cannabinoids, establishing Clz9 and Tcz9 as promising biocatalysts for broad-scale cannabinoid production. Second, I will discuss how access to CBC-type cannabinoids has enabled discovery of new interaction landscapes at the intersection of lipid signalling GPCR biology, underscoring how much remains to be learned of both endo- and phytocannabinoid biology.
Biography:
Dr. Anna Love is an NIH Ruth Kirschstein-NRSA postdoctoral fellow in Prof. Bradley Moore’s laboratory at the Scripps Institution of Oceanography at UCSD. Here, she characterizes and engineers unique enzymes involved in marine natural products biosynthesis for production of neuroactive small molecules, and studies their effects in the brain. Before her postdoctoral appointment, Dr. Love completed graduate work at the University of California, Irvine in the lab of Prof. Jennifer Prescher. Her doctoral thesis focused on developing new chemical tools and synthetic biology strategies for non-invasive monitoring of biological processes. Her current research interests lie in co-opting natural products and their biosynthetic machinery to evolve, develop and apply new tool compounds and therapeutics to expand our molecular understanding of neurological disease.
Biosynthesis and biological mechanisms of minor cannabinoids
Abstract :
The study of natural products has enabled major insights into the biology of the brain, from discovery of new classes of receptors, to therapeutic starting points for neurological disease. For example, the endocannabinoid system, a signalling network comprising two receptors and a handful of bioactive lipids, was discovered through investigations into the molecular basis for Cannabis psychoactivity from Δ9-tetrahydrocannabinol (Δ9-THC). However, much remains to be learned about plant cannabinoids (phytocannabinoids) beyond Δ9-THC and cannabidiol (CBD), two of >110 cannabinoids produced in plants, and the physiological intersections of endo- and phytocannabinoid biology, including whether such interactions can be taken advantage of for selective pharmacological manipulation. First, I will address access to plant cannabinoids beyond Δ9-THC and CBD, which are generated natively in low quantities, and thus referred to as “minor cannabinoids.” I discovered that two marine bacterial flavoenzymes, Clz9 and Tcz9, possessed the unique ability to perform electrocyclization chemistry to generate the minor cannabinoid, cannabichromene (CBC) and analogues with high yield in bacteria. This provides a complementary route to isolation or synthetic chemistry to access material. Structural and mechanistic analysis revealed unique biochemistry governing the cannabinoid-cyclization chemistry of Clz9 and Tcz9, and established their utility as new members of the berberine-bridge like enzyme family. Complementary substrate-level engineering and active site restructuring improved the stereoselectivity of CBC-formation, providing enantiopure material. Further enzyme engineering efforts guided by a substrate-bound structure and a high-throughput screening platform seek to repurpose Clz9 and Tcz9 for production of cannabinoids beyond CBC, including THC-type and CBD-type cannabinoids, establishing Clz9 and Tcz9 as promising biocatalysts for broad-scale cannabinoid production. Second, I will discuss how access to CBC-type cannabinoids has enabled discovery of new interaction landscapes at the intersection of lipid signalling GPCR biology, underscoring how much remains to be learned of both endo- and phytocannabinoid biology.
Biography:
Dr. Anna Love is an NIH Ruth Kirschstein-NRSA postdoctoral fellow in Prof. Bradley Moore’s laboratory at the Scripps Institution of Oceanography at UCSD. Here, she characterizes and engineers unique enzymes involved in marine natural products biosynthesis for production of neuroactive small molecules, and studies their effects in the brain. Before her postdoctoral appointment, Dr. Love completed graduate work at the University of California, Irvine in the lab of Prof. Jennifer Prescher. Her doctoral thesis focused on developing new chemical tools and synthetic biology strategies for non-invasive monitoring of biological processes. Her current research interests lie in co-opting natural products and their biosynthetic machinery to evolve, develop and apply new tool compounds and therapeutics to expand our molecular understanding of neurological disease.
Practical information
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- Free