Jai Yeong Ju.

Post-Doctorate Researcher
University of California, Berkeley

Ph.D. Biotechnology, 1998
Yonsei University

M.S. Food & Biotechnology, 1993
Yonsei University


Office Location: 497A Tan Hall
Office Telephone: 510-643-8340
Office Fax: 510-643-1228

Novel Anticholesterol Agent from Marine Isoprenoids

The biosynthesis of cholesterol is a complex process subject to upstream and downstream regulation mechanisms, some of which are not well understood. A key enzyme in this pathway is HMG-CoA reductase. This enzyme catalyzes the conversion of HMG-CoA to mevalonate, which is an early and rate limiting step in the biosynthesis of cholesterol. Much effort has been spent on developing direct inhibitors of this enzyme, culminating in the approval of the drug Lovastatin (a.k.a. Mevacor, with a yearly market of ca. $750 million). However, other enzymes, which are involved in later steps and are more specific to cholesterol synthesis (e.g., squalene synthetase, squalene epoxidase, and oxidosqualene synthase), are also potential targets for new drugs that avoid the side effects of a long term Lovastatin uptake.

We plan to derivatize of unique marine isoprenoids, isolated from the deep-sea extremophile Methanococcus jannaschii, to generate and screen libraries of compounds with potential activity as anticholesterol agents. The approach consists of initially developing a pattern of cyclization of squalene, the isoprenoid precursor of cholesterol, and then extending it to the novel marine isoprenoids. Enaymztic cyclization of these compounds is expected to produce novel steroids and sterols, which are of interest as potential inhibitors of HMG-CoA reductase. The enzymatic cyclization products will also serve as lead compounds for further modification and optimization by chemical methods.