Date of Award


Document Type

Campus Access Thesis

Degree Name

Master of Science (MS)



First Advisor

Daniel P Dowling

Second Advisor

Bela Torok

Third Advisor

Jason Evans


The incorporation of thiazoline-based heterocycles into natural products is of great interest for the bioengineering of biosynthetic systems to develop novel compounds, and biosynthesis will also be a greener pathway for the synthesis of complex compounds compared to organic synthetic methods. This thesis focuses on the cyclization domains and docking domains in hybrid polyketide synthase (PKS)/nonribosomal peptide synthetase (NRPS) systems, using the biosynthetic pathways of epothilones and yersiniabactin as models. The cyclization domains in NRPSs are responsible for the generation of heterocycles, by preforming both condensation and cyclization reactions. Here we present the crystallization of YbtCy2, initial X-ray diffraction data and progress towards determining the crystal structures of the three cyclization domains from yersiniabactin synthetase, and also work towards studying the activity of the cyclization domain chemical mechanism. In addition, we are studying the structural features of the EpoB docking domain (EpoBdd), which is responsible for protein-protein communication in hybrid PKS/NRPS systems.


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