- Advisor: Yi Tang
- Department: Chemical and Biomolecular Engineering
- Campus: UCLA
- BioPACIFIC MIP Research: SET 1 - Bioderived Materials
What is your research focus?
We have elucidated a biosynthetic gene pathway consisting of a highly-reducing polyketide synthase (HRPKS), a non-reducing polyketide synthase (NRPKS), and a thioesterase (TE) in the fungus Metarhizium anisopliae that produces olivetolic acid as well as different olivetolic acid analogs. We have also elucidated homologous clusters that produce olivetolic acid and some analogs. Olivetolic acid is a key intermediate, predominately found in the cannabis plant, in the biosynthesis of delta-9-tetrahydracannabinol (∆9-THC) and cannabidiol (CBD). Additionally, olivetolic acid itself is proposed to possibly have antimicrobial, cytotoxic, antifungal, and photoprotective properties. Therefore, we want to genome mine for similar biosynthetic clusters in fungi as well as utilize a high throughput screening method where we can test many mutations in the ketosynthase (KS) domain of the HRPKS in order to produce rare, new to nature olivetolic acid analogs that can then be further processed to rare, new to nature cannabinoids. The ketosynthase domain in the HRPKS is responsible for decarboxylative Claisen condensation adding a two- carbon keto unit to the growing acyl chain. We plan to utilize the Living BioFoundry to generate hundreds of KS mutations which we hypothesize will produce olivetolic acid analogs of various alkyl chain lengths. We will then perform bioactivity assays on these analogs in addition to the elaborated cannabinoids further downstream of the pathway. Due to this, I believe this project fits in with the BioPACIFIC MIP mission to utilize bio-derived building blocks from microorganisms like fungi to build materials with powerful potential to impact our world.
What excites you about NSF BioPACIFIC MIP?
I’ve had the pleasure to be a BioPACIFIC MIP Fellow in the previous cycle and I greatly enjoyed learning from a multidisciplinary group of experts in a variety of fields such as synthetic biology, synthetic chemistry, molecular biology, biomaterials characterization, and biosynthesis. Additionally, I was blessed with the opportunity to begin writing and implementing protocols using the Living BioFoundry and I definitely would like to continue what I have started. Being a BioPACIFIC MIP Fellow provides a great opportunity to collaborate with labs not only on UCLA campus but on UCSB’s campus. For example, I have been able to talk with and exchange ideas with Laza Butkovich from the Michelle O’Malley lab at USCB. Last year, I wrote that I strongly believed that becoming a BioPACIFIC MIP Fellow would enhance my PhD experience by equipping me with the tools to expand my research outside my current discipline and I have found that to be the case. I would like to become a BioPACIFIC MIP Fellow once again to continue to grow my interdisciplinary research skills and learn from experts in a variety of fields.