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Lyman L. Handy Colloquium Series




Production of A Blockbuster Drug Using Biocatalysis
 

Professor Yi Tang
Department of Chemical and Biomolecular Engineering
University of California, Los Angeles
Los Angeles, CA 90095

Abstract

Simvastatin (Zocor) is a blockbuster drug used towards the treatment of hypercholesterolemia . Simvastatin exhibits potent inhibitory activity towards hydroxymethylglutaryl coenzyme A reductase (HMGR), the rate-limiting step of cholesterol biosynthesis. We have developed an Escherichia coli-based, whole-cell biocatalytic process that can convert a precursor molecule Monacolin J (MJ) to simvastatin in one-step, utilizing a readily available dimethylbutyryl thioester substrate. The enzyme that catalyzes the conversion is the acyltransferase LovD from Aspergillus terreus. In this presentation, we will present recent metabolic engineering and protein engineering work that have resulted in significant enhancement in the efficiency and throughput of the whole cell system. The biocatalytic process has been scaled to 30,000L fermentations in the production of genetic simvastatin drugs.  

Bio 
Yi Tang received his B.S in Chemical Engineering and Material Science from Pennsylvania State University in 1997, his Ph.D. in Chemical Engineering from Caltech in 2002 under the mentoring of Prof. David Tirrell.  As a postdoctoral fellow, he worked with Prof. Chaitan Khosla at Stanford University.  He is currently an Associate Professor at the Department of Chemical and Biomolecular Engineering at UCLA (since 2004) and his research lab is focused on natural product biosynthesis, biocatalysis and nanobiotechnology.  He has received numerous awards for his research, including the Packard Fellowship, Sloan Fellowship, and recently the AIChE Allan P. Colburn Award.

 

Time and Location

Thursday, November 5, 2009
Seminar at 12:45p.m.
SLH 100
The Scientific Community is Cordially Invited.