News and Events
Fall 2009 Seminars
Production of A Blockbuster Drug Using Biocatalysis
Yi Tang
Chemical and Biomolecular Engineering
University of California, Los Angeles
Thursday, December 3, 2009
10:00 - 11:00 a.m.
102 Chemistry Building
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.