- Advisor: Yi Tang
- Department: Bioengineering
- Campus: UCLA
- BioPACIFIC MIP Research: SET 1 - Bioderived Materials
What is your research focus?
My research focuses on biosynthesis of monoterpene indole alkaloids, a structurally complex class of plant compounds with high therapeutic value, in yeast. I have reconstituted the strictosidine (universal precursor to MIAs) pathway in yeast that produces ~100 mg/L de novo. This aligns with SET 1 on microbial production of valuable molecules from complex biosynthetic pathways, difficult to attain artificially. I am applying metabolic engineering tools to optimize production and push biosynthesis towards MIAs. Yeast is genetically tractable and shares a common endomembrane system with plants, making it suitable for achieving, otherwise inaccessible, high titer production of structurally complex and diverse MIAs.
A current bottleneck is the inefficiency of strictosidine glucosidase (SGD), responsible for deglucosylation of strictosidine,. To address this, we aim to generate a library of enzyme mutants to introduce to our microbial platform followed by selection of strains with improved desired phenotype. We are collaborating with Professor Di Carlo’s lab to develop a high-throughput screening method to sort strains via PicoShell Encapsulation and Fluorescent Activated Cell Sorting using the pathway-related molecule, alstonine (Ex. 350nm, Em. 470nm), as a probe for sorting phenotypic variants correlating with strictosidine and post-SGD titers. Our method can be universally applied to any vector library, including CRISPR-mediated regulation of host metabolism, substantially facilitating discovery of optimal global balance of endogenous and heterologous pathways. This aligns with SET 1 aim of evolving enzymes to catalyze synthesis of complex molecules with potential to be applied towards unnatural synthesis of novel compounds with enhanced and/or unlocked bioactivity.
What excites you about NSF BioPACIFIC MIP?
I am interested in the BioPACIFIC MIP program because my research aligns remarkably well with the in-house research described in SET 1, and I want to foster new connections with others in related fields. I have had a strong interest in interdisciplinary chemical biology/enginering research as reflected by my background in both chemical and bioengineering as well as biotechnology-related disciplines. I have been involved and excited by natural product biosynthesis for 5 years, and I want to take my research to the next level by taking advantage of the networking opportunities, professional development and unique perspectives, ideas and innovative technology I will be exposed to through this program. I already currently take advantage of BioPACIFIC MIP technology housed in CNSI at UCLA, as I am currently making use of Triple Quadrupole for metabolic analysis and currently being trained on the automated recombinant DNA technology in the Living Biofoundry lab. These experiences have made me appreciative and excited by the opportunities that BioPACIFIC MIP offers to uniquely enhance my biosynthesis research!