Bryostatins are polyketide secondary metabolites isolated from the marine bryozoan Bugula neritina. Bryostatin 1 is a very promising anti-cancer drug, and is currently undergoing Phase II clinical trials. Unfortunately, bryostatin concentrations in B. neritina are very low and, to date, there are no chemical synthetic alternatives, requiring the harvest of large amounts of the animal to obtain sufficient quantities of bryostatin for biotesting. Recent research has revealed that the bryostatins are produced by the bacterial endosymbiont, Endobugula sertula, but attempts to culture the microbe have not been successful. Consequently, the latest research effort has resulted in the identification of a polyketide synthase (PKS) gene cluster from symbiont-enriched DMA that may be responsible for bryostatin biosynthesis. However, as the organism cannot be cultured, mutation and complementation experiments that can verify whether this cluster produces bryostatin cannot be conducted. In this project, I propose to use in vitro studies with purified putative bryostatin PKS modules to determine whether this gene cluster is in fact responsible for the production of bryostatin. This research may lead to production of bryostatin by a heterologous host.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32CA110636-02
Application #
7076825
Study Section
Special Emphasis Panel (ZRG1-F04A (20))
Program Officer
Lohrey, Nancy
Project Start
2005-06-01
Project End
2008-05-31
Budget Start
2006-06-01
Budget End
2007-05-31
Support Year
2
Fiscal Year
2006
Total Cost
$50,428
Indirect Cost
Name
University of Michigan Ann Arbor
Department
Pharmacology
Type
Schools of Pharmacy
DUNS #
073133571
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109