Hang, Leibniz

Leibniz is a student in the Chemistry Graduate Program, where he works in the laboratory of Dr. Yi Tang.  He joined the CMB training program in 2016.  He received a B.S. (2010) and M.S. degree (2012) from the University of California, San Diego.

Mentor: Dr. Yi Tang

Research project:

Polyketide-based pharmaceuticals compose some of the most important drugs in the world. These natural products exhibit a significantly higher likelihood of commercialization. Although polyketides constitute the most abundant secondary metabolite, the highly-reducing polyketide synthases (HR-PKSs) remain poorly understood. Genome sequencing efforts suggest that only a small fraction of fungal polyketides and HR-PKSs have been harvested. Accessing the remaining chemical space offers exciting possibilities towards the research development and engineering of polyketides.

An overarching objective of my research project involves the correlation between protein sequence and polyketide chemical structure. Using phylogenetic classifications and bioinformatics analyses, fungal genomes will be mined for HR-PKS genes for heterologous expression. Furthermore, in vitro experiments with purified endogenous and mutant HR-PKS enzymes can characterize the effects of the catalytic domains on the compound structure. Synthetic chemical probes that mimic biosynthetic intermediates also offer additional insight into the kinetic parameters of the HR-PKS enzymes. In total, my research project details the genomic search, heterologous expression, biochemical characterization and genetic engineering of HR-PKS enzymes.