Xavier Tao

Expanding a Computational Platform for the Engineering of Chimeric Polyketide Synthases

Polyketide synthases (PKSs) are a family of enzyme complexes that synthesize a diverse class of secondary metabolites including clinically important antibiotic, antifungal, and anticancer compounds. In order to accomplish this, PKSs utilize a modular assembly with a wide variety of catalytic building blocks, passing molecular intermediates between modules until a product is finished. Due to their unique modular nature and deterministic mechanisms, PKSs have inspired engineering efforts to biosynthesize various useful new molecules. However, designing active variants still face difficulties due to a lack of understanding for the reasons behind successful or inactive enzymes, frequently resulting in nonfunctional systems. For this reason, my project will expand ClusterCAD, a computational platform that provides sequence and structure search tools useful for identifying parts necessary to build new chimeric PKSs. Specifically, I will annotate new database entries and implement support for irregular catalytic modules. The addition of novel mechanism elucidations and support for new and unusual catalytic domains will ultimately enhance the platform’s ability to guide the engineering of chimeric PKSs.

Message to Sponsor

Thank you very much to SURF and the Rose Hills Foundation for funding my project! This fellowship will not only enable me to apply my knowledge from coursework and other experiences to a comprehensive research project, but also to learn more about computational biology and its applications. I truly appreciate this opportunity to both develop my skills as a researcher and contribute to a computational platform beneficial to numerous other researchers.
  • Major: Chemical Biology
  • Sponsor: Rose Hill Foundation
  • Mentor: Tyler Backman