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There is now a CONTENT FREEZE for Mercury while we switch to a new platform. It began on Friday, March 10 at 6pm and will end on Wednesday, March 15 at noon. No new content can be created during this time, but all material in the system as of the beginning of the freeze will be migrated to the new platform, including users and groups. Functionally the new site is identical to the old one. webteam@gatech.edu
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Prof. Barbara Gerratana, University of Maryland
Biosynthesis of Pyrrolobenzodiazepines, naturally produced antitumor compounds
Biochemistry Division Seminar Series (joint with Georgia State University)
Pyrrolo[1,4]benzodiazepines (PBDs), produced by actinomycetes, are sequence selective DNA alkylating agents with anti-tumor and antibiotic properties. Sibiromycin and tomaymycin are two naturally produced PBDs. Sibiromycin is the most potent naturally produced PBDs and only one of two available glycosylated PBDs. Tomaymycin was used as the template for SJG-136, a synthetic PBD dimer. Phase I clinical trials of SJG-136 have been successful for the treatment of metastatic or unresectable solid tumors. We have identified and sequenced the tomaymycin and sibiromycin gene clusters. We have confirmed the assignment of the gene clusters and identified their boundaries. Using gene inactivation and chemical complementation experiments we have elucidated the biosynthetic pathway for the anthranilate moiety of sibiromycin and tomaymycin. Initial in vitro characterization of the biosynthetic enzymes involved in the unusual tyrosine to pyrrole transformation will be presented.
For more information contact Prof. Wendy Kelly (404-385-1154).
